Sample records for nanostructures encapsulating gentamicin

  1. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    NASA Astrophysics Data System (ADS)

    Jain-Gupta, Neeta; Pothayee, Nipon; Pothayee, Nikorn; Tyler, Ronald; Caudell, David L.; Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S.; Sriranganathan, Nammalwar

    2013-11-01

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30-32 weight percentage of gentamicin. The zeta potential changed from -39 to -13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log10), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log10). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B. melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

  2. K88 Fimbrial Adhesin Targeting of Microspheres Containing Gentamicin Made with Albumin Glycated with Lactose.

    PubMed

    Sarabia-Sainz, Andre-I; Sarabia-Sainz, Hector Manuel; Montfort, Gabriela Ramos-Clamont; Mata-Haro, Veronica; Guzman-Partida, Ana María; Guzman, Roberto; Garcia-Soto, Mariano; Vazquez-Moreno, Luz

    2015-09-16

    The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88) was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1) galactose) was used as the microsphere matrix (MS-Lac) and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3) were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10-17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections.

  3. K88 Fimbrial Adhesin Targeting of Microspheres Containing Gentamicin Made with Albumin Glycated with Lactose

    PubMed Central

    Sarabia-Sainz, Andre-i; Sarabia-Sainz, Hector Manuel; Ramos-Clamont Montfort, Gabriela; Mata-Haro, Veronica; Guzman-Partida, Ana María; Guzman, Roberto; Garcia-Soto, Mariano; Vazquez-Moreno, Luz

    2015-01-01

    The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88) was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1) galactose) was used as the microsphere matrix (MS-Lac) and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3) were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10–17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections. PMID:26389896

  4. Synthesis of selenium nano-composite (t-Se@PS) by surface initiated atom transfer radical polymerization.

    PubMed

    Wang, Michael C P; Gates, Byron D

    2012-09-04

    Selenium nanostructures, which are otherwise susceptible to oxidative damage, were encapsulated with a thin layer of polystyrene. The thin layer of polystyrene was grafted onto the surfaces of selenium by a surface initiated atom transfer radical polymerization reaction. These encapsulated nanostructures demonstrate an enhanced resistance towards corrosion.

  5. SERS active Ag encapsulated Fe@SiO2 nanorods in electromagnetic wave absorption and crystal violet detection.

    PubMed

    Senapati, Samarpita; Srivastava, Suneel Kumar; Singh, Shiv Brat; Kulkarni, Ajit R

    2014-11-01

    The present work is focused on the preparation of Fe nanorods by the chemical reduction of FeCl3 (aq) using NaBH4 in the presence of glycerol as template followed by annealing of the product at 500°C in the presence of H2 gas flow. Subsequently, its surface has been modified by silica followed by silver nanoparticles to form silica coated Fe (Fe@SiO2) and Ag encapsulated Fe@SiO2 nanostructure employing the Stöber method and silver mirror reaction respectively. XRD pattern of the products confirmed the formation of bcc phase of iron and fcc phase of silver, though silica remained amorphous. FESEM images established the growth of iron nanorods from the annealed product and also formation of silica and silver coating on its surface. The appearance of the characteristics bands in FTIR confirmed the presence of SiO2 on the Fe surface. Magnetic measurements at room temperature indicated the ferromagnetic behavior of as prepared iron nanorods, Fe@SiO2 and silver encapsulated Fe@SiO2 nanostructures. All the samples exhibited strong microwave absorption property in the high frequency range (10GHz), though it is superior for Ag encapsulated Fe@SiO2 (-14.7dB) compared with Fe@SiO2 (-9.7dB) nanostructures of the same thickness. The synthesized Ag encapsulated Fe@SiO2 nanostructure also exhibited the SERS phenomena, which is useful in the detection of the carcinogenic dye crystal violet (CV) upto the concentration of 10(-10)M. All these findings clearly demonstrate that the Ag encapsulated Fe@SiO2 nanostructure could efficiently be used in the environmental remediation. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Assembly of ordered carbon shells on semiconducting nanomaterials

    DOEpatents

    Sutter, Eli Anguelova; Sutter, Peter Werner

    2010-05-11

    In some embodiments of the invention, encapsulated semiconducting nanomaterials are described. In certain embodiments the nanostructures described are semiconducting nanomaterials encapsulated with ordered carbon shells. In some aspects a method for producing encapsulated semiconducting nanomaterials is disclosed. In some embodiments applications of encapsulated semiconducting nanomaterials are described.

  7. Assembly of ordered carbon shells on semiconducting nanomaterials

    DOEpatents

    Sutter, Eli Anguelova; Sutter, Peter Werner

    2012-10-02

    In some embodiments of the invention, encapsulated semiconducting nanomaterials are described. In certain embodiments the nanostructures described are semiconducting nanomaterials encapsulated with ordered carbon shells. In some aspects a method for producing encapsulated semiconducting nanomaterials is disclosed. In some embodiments applications of encapsulated semiconducting nanomaterials are described.

  8. Lipid Membrane Encapsulation of a 3D DNA Nano Octahedron.

    PubMed

    Perrault, Steven D; Shih, William M

    2017-01-01

    Structural DNA nanotechnology methods such as DNA origami allow for the synthesis of highly precise nanometer-scale materials (Rothemund, Nature 440:297-302, 2006; Douglas et al., Nature 459:414-418, 2009). These offer compelling advantages for biomedical applications. Such materials can suffer from structural instability in biological environments due to denaturation and nuclease digestion (Hahn et al., ACS Nano 2014; Perrault and Shih, ACS Nano 8:5132-5140, 2014). Encapsulation of DNA nanostructures in a lipid membrane compartmentalizes them from their environment and prevents denaturation and nuclease digestion (Perrault and Shih, ACS Nano 8:5132-5140, 2014). Here, we describe the encapsulation of a 50 nm DNA nanostructure having the geometry of a wireframe octahedron in a phospholipid membrane containing poly-(ethylene glycol), resulting in biocompatible DNA nanostructures.

  9. Synthesis of fullerene@gold core-shell nanostructures.

    PubMed

    Ren, Yupeng; Paira, Priyankar; Nayak, Tapas Ranjan; Ang, Wee Han; Pastorin, Giorgia

    2011-07-21

    A "direct encapsulation" method was developed for the synthesis of highly stable water-soluble fullerene@gold core-shell nanostructures, with gold nanoshells showing either closed or porous morphology. This gold nano-shell coating formed a "nano-oven", capable of decomposing encapsulated fullerene molecules rapidly when irradiated by laser. We envisaged this being a useful tool for chemical reactions as well as a novel scaffold for nano-material synthesis.

  10. Designing deoxidation inhibiting encapsulation of metal oxide nanostructures for fluidic and biological applications

    NASA Astrophysics Data System (ADS)

    Ghosh, Moumita; Ghosh, Siddharth; Seibt, Michael; Schaap, Iwan A. T.; Schmidt, Christoph F.; Mohan Rao, G.

    2016-12-01

    Due to their photoluminescence, metal oxide nanostructures such as ZnO nanostructures are promising candidates in biomedical imaging, drug delivery and bio-sensing. To apply them as label for bio-imaging, it is important to study their structural stability in a bio-fluidic environment. We have explored the effect of water, the main constituent of biological solutions, on ZnO nanostructures with scanning electron microscopy (SEM) and photoluminescence (PL) studies which show ZnO nanorod degeneration in water. In addition, we propose and investigate a robust and inexpensive method to encapsulate these nanostructures (without structural degradation) using bio-compatible non-ionic surfactant in non-aqueous medium, which was not reported earlier. This new finding is an immediate interest to the broad audience of researchers working in biophysics, sensing and actuation, drug delivery, food and cosmetics technology, etc.

  11. Improvement of curcuminoid bioaccessibility from turmeric by a nanostructured lipid carrier system.

    PubMed

    Park, Sung Jin; Garcia, Coralia V; Shin, Gye Hwa; Kim, Jun Tae

    2018-06-15

    Turmeric contains curcumin and its analogues, which show anticancer and antiinflammatory effects; however, curcuminoids are lipophilic and are poorly absorbed by the human body. Nanostructured lipid carriers for encapsulating whole turmeric powder were successfully produced by ultrasonication, and their physicochemical properties and stability in simulated gastric and intestinal media were evaluated. The turmeric nanostructured lipid carriers (TNLCs) exhibited a round shape, small diameter (282 ± 7.19 nm), adequate zeta potential (-22.75 ± 1.20 mV), and high encapsulation efficiency (93.3 ± 0.01%). The TNLCs were able to protect the encapsulated curcuminoids under acidic gastric conditions, and effectively released 95 ± 2.51% of the curcuminoids in the simulated intestinal medium, demonstrating their suitability for controlled release. The in vitro bioaccessibility of the encapsulated curcuminoids was 75 ± 1.24%, representing more than a fourfold increase compared to that of free turmeric. Therefore, the proposed TNLCs are a promising delivery system for increasing the bioaccessibility of curcuminoids from turmeric. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. An inorganic capping strategy for the seeded growth of versatile bimetallic nanostructures

    DOE PAGES

    Pei, Yuchen; Maligal-Ganesh, Raghu V.; Xiao, Chaoxian; ...

    2015-09-11

    Metal nanostructures have attracted great attention in various fields due to their tunable properties through precisely tailored sizes, compositions and structures. Using mesoporous silica (mSiO 2) as the inorganic capping agent and encapsulated Pt nanoparticles as the seeds, we developed a robust seeded growth method to prepare uniform bimetallic nanoparticles encapsulated in mesoporous silica shells (PtM@mSiO 2, M = Pd, Rh, Ni and Cu). Unexpectedly, we found that the inorganic silica shell is able to accommodate an eight-fold volume increase in the metallic core by reducing its thickness. The bimetallic nanoparticles encapsulated in mesoporous silica shells showed enhanced catalytic propertiesmore » and thermal stabilities compared with those prepared with organic capping agents. As a result, this inorganic capping strategy could find a broad application in the synthesis of versatile bimetallic nanostructures with exceptional structural control and enhanced catalytic properties.« less

  13. Controlled synthesis of carbon-encapsulated copper nanostructures by using smectite clays as nanotemplates.

    PubMed

    Tsoufis, Theodoros; Colomer, Jean-François; Maccallini, Enrico; Jankovič, Lubos; Rudolf, Petra; Gournis, Dimitrios

    2012-07-23

    Rhomboidal and spherical metallic-copper nanostructures were encapsulated within well-formed graphitic shells by using a simple chemical method that involved the catalytic decomposition of acetylene over a copper catalyst that was supported on different smectite clays surfaces by ion-exchange. These metallic-copper nanostructures could be separated from the inorganic support and remained stable for months. The choice of the clay support influenced both the shape and the size of the synthesized Cu nanostructures. The synthesized materials and the supported catalysts from which they were produced were studied in detail by TEM and SEM, powder X-ray diffraction, thermal analysis, as well as by Raman and X-ray photoelectron spectroscopy. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Encapsulated Annealing: Enhancing the Plasmon Quality Factor in Lithographically–Defined Nanostructures

    PubMed Central

    Bosman, Michel; Zhang, Lei; Duan, Huigao; Tan, Shu Fen; Nijhuis, Christian A.; Qiu, Cheng–Wei; Yang, Joel K. W.

    2014-01-01

    Lithography provides the precision to pattern large arrays of metallic nanostructures with varying geometries, enabling systematic studies and discoveries of new phenomena in plasmonics. However, surface plasmon resonances experience more damping in lithographically–defined structures than in chemically–synthesized nanoparticles of comparable geometries. Grain boundaries, surface roughness, substrate effects, and adhesion layers have been reported as causes of plasmon damping, but it is difficult to isolate these effects. Using monochromated electron energy–loss spectroscopy (EELS) and numerical analysis, we demonstrate an experimental technique that allows the study of these effects individually, to significantly reduce the plasmon damping in lithographically–defined structures. We introduce a method of encapsulated annealing that preserves the shape of polycrystalline gold nanostructures, while their grain-boundary density is reduced. We demonstrate enhanced Q–factors in lithographically–defined nanostructures, with intrinsic damping that matches the theoretical Drude damping limit. PMID:24986023

  15. Advances in structural design of lipid-based nanoparticle carriers for delivery of macromolecular drugs, phytochemicals and anti-tumor agents.

    PubMed

    Angelova, Angelina; Garamus, Vasil M; Angelov, Borislav; Tian, Zhenfen; Li, Yawen; Zou, Aihua

    2017-11-01

    The present work highlights recent achievements in development of nanostructured dispersions and biocolloids for drug delivery applications. We emphasize the key role of biological small-angle X-ray scattering (BioSAXS) investigations for the nanomedicine design. A focus is given on controlled encapsulation of small molecular weight phytochemical drugs in lipid-based nanocarriers as well as on encapsulation of macromolecular siRNA, plasmid DNA, peptide and protein pharmaceuticals in nanostructured nanoparticles that may provide efficient intracellular delivery and triggered drug release. Selected examples of utilisation of the BioSAXS method for characterization of various types of liquid crystalline nanoorganizations (liposome, spongosome, cubosome, hexosome, and nanostructured lipid carriers) are discussed in view of the successful encapsulation and protection of phytochemicals and therapeutic biomolecules in the hydrophobic or the hydrophilic compartments of the nanocarriers. We conclude that the structural design of the nanoparticulate carriers is of crucial importance for the therapeutic outcome and the triggered drug release from biocolloids. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Gentamicin Sulfate PEG-PLGA/PLGA-H Nanoparticles: Screening Design and Antimicrobial Effect Evaluation toward Clinic Bacterial Isolates

    PubMed Central

    Dorati, Rossella; DeTrizio, Antonella; Spalla, Melissa; Migliavacca, Roberta; Pagani, Laura; Pisani, Silvia; Chiesa, Enrica; Modena, Tiziana; Genta, Ida

    2018-01-01

    Nanotechnology is a promising approach both for restoring or enhancing activity of old and conventional antimicrobial agents and for treating intracellular infections by providing intracellular targeting and sustained release of drug inside infected cells. The present paper introduces a formulation study of gentamicin loaded biodegradable nanoparticles (Nps). Solid-oil-in water technique was studied for gentamicin sulfate nanoencapsulation using uncapped Polylactide-co-glycolide (PLGA-H) and Polylactide-co-glycolide-co-Polyethylenglycol (PLGA-PEG) blends. Screening design was applied to optimize: drug payload, Nps size and size distribution, stability and resuspendability after freeze-drying. PLGA-PEG concentration resulted most significant factor influencing particles size and drug content (DC): 8 w/w% DC and 200 nm Nps were obtained. Stirring rate resulted most influencing factor for size distribution (PDI): 700 rpm permitted to obtain homogeneous Nps dispersion (PDI = 1). Further experimental parameters investigated, by 23 screening design, were: polymer blend composition (PLGA-PEG and PLGA-H), Polyvinylalcohol (PVA) and methanol concentrations into aqueous phase. Drug content was increased to 10.5 w/w%. Nanoparticle lyophilization was studied adding cryoprotectants, polyvinypirrolidone K17 and K32, and sodiumcarboxymetylcellulose. Freeze-drying protocol was optimized by a mixture design. A freeze-dried Nps powder free resuspendable with stable Nps size and payload, was developed. The powder was tested on clinic bacterial isolates demonstrating that after encapsulation, gentamicin sulfate kept its activity. PMID:29329209

  17. Nanostructured Catalytic Hybrid Materials for Energy Conversion or Storage

    DTIC Science & Technology

    2017-08-27

    and 6) and characterized them using bomb calorimetry, DSC and XRD. - We are organizing the data to make research articles and patents. [Iron...Unlimited Distribution Figure 4 • Bomb calorimeter (BC) enthalpy plot of Al-encapsulated nanofibers Nanostructured catalytic hybrid materials for energy

  18. Nanostructured Lipid Carriers (NLC) as Vehicles for Topical Administration of Sesamol: In Vitro Percutaneous Absorption Study and Evaluation of Antioxidant Activity.

    PubMed

    Puglia, Carmelo; Lauro, Maria Rosaria; Offerta, Alessia; Crascì, Lucia; Micicchè, Lucia; Panico, Anna Maria; Bonina, Francesco; Puglisi, Giovanni

    2017-03-01

    Sesamol is a natural phenolic compound extracted from Sesamum indicum seed oil. Sesamol is endowed with several beneficial effects, but its use as a topical agent is strongly compromised by unfavorable chemical-physical properties. Therefore, to improve its characteristics, the aim of the present work was the formulation of nanostructured lipid carriers as drug delivery systems for topical administration of sesamol.Two different nanostructured lipid carrier systems have been produced based on the same solid lipid (Compritol® 888 ATO) but in a mixture with two different kinds of oil phase such as Miglyol® 812 (nanostructured lipid carrier-M) and sesame oil (nanostructured lipid carrier-PLUS). Morphology and dimensional distribution of nanostructured lipid carriers have been characterized by differential scanning calorimetry and photon correlation spectroscopy, respectively. The release pattern of sesamol from nanostructured lipid carriers was evaluated in vitro determining drug percutaneous absorption through excised human skin. Furthermore, an oxygen radical absorbance capacity assay was used to determine their antioxidant activity.From the results obtained, the method used to formulate nanostructured lipid carriers led to a homogeneous dispersion of particles in a nanometric range. Sesamol has been encapsulated efficiently in both nanostructured lipid carriers, with higher encapsulation efficiency values (> 90 %) when sesame oil was used as the oil phase (nanostructured lipid carrier-PLUS). In vitro evidences show that nanostructured lipid carrier dispersions were able to control the rate of sesamol diffusion through the skin, with respect to the reference formulations.Furthermore, the oxygen radical absorbance capacity assay pointed out an interesting and prolonged antioxidant activity of sesamol, especially when vehiculated by nanostructured lipid carrier-PLUS. Georg Thieme Verlag KG Stuttgart · New York.

  19. pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional Assemblies

    DOE PAGES

    Moyer, Tyson J.; Finbloom, Joel A.; Chen, Feng; ...

    2014-10-13

    Supramolecular self-assembly offers promising new ways to control nanostructure morphology and respond to external stimuli. A pH-sensitive self-assembled system was developed to both control nanostructure shape and respond to the acidic microenvironment of tumors using self-assembling peptide amphiphiles (PAs). Here, by incorporating an oligo-histidine H 6 sequence, we developed two PAs that self-assembled into distinct morphologies on the nanoscale, either as nanofibers or spherical micelles, based on the incorporation of the aliphatic tail on the N-terminus or near the C-terminus, respectively. Both cylinder and sphere-forming PAs demonstrated reversible disassembly between pH 6.0 and 6.5 upon protonation of the histidine residuesmore » in acidic solutions. These PAs were then characterized and assessed for their potential to encapsulate hydrophobic chemotherapies. The H 6-based nanofiber assemblies encapsulated camptothecin (CPT) with up to 60% efficiency, a 7-fold increase in CPT encapsulation relative to spherical micelles. Additionally, pH-sensitive nanofibers showed improved tumor accumulation over both spherical micelles and nanofibers that did not change morphologies in acidic environments. We have demonstrated that the morphological transitions upon changes in pH of supramolecular nanostructures affect drug encapsulation and tumor accumulation. Lastly, our findings also suggest that these supramolecular events can be tuned by molecular design to improve the pharmacologic properties of nanomedicines.« less

  20. In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration

    NASA Astrophysics Data System (ADS)

    Yue, Xinxin; Niu, Mao; Zhang, Te; Wang, Cheng; Wang, Zhonglei; Wu, Wangxi; Zhang, Qi; Lai, Chunhua; Zhou, Lei

    2016-03-01

    Alveolar bone loss has long been a challenge in clinical dental implant therapy. Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone. However, the successful use of SV to increase bone formation in vivo largely depends on the local concentration of SV at the site of action, and there have been continuing efforts to develop an appropriate delivery system. Specifically, nanostructured lipid carrier (NLC) systems have become a popular type of encapsulation carrier system. Therefore, SV-loaded NLCs (SNs) (179.4 nm in diameter) were fabricated in this study, and the osteogenic effect of the SNs was evaluated in a critical-sized rabbit calvarial defect. Our results revealed that the SNs significantly enhanced bone formation in vivo, as evaluated by hematoxylin and eosin (HE) staining, immunohistochemistry, and a fluorescence analysis. Thus, this novel nanostructured carrier system could be a potential encapsulation carrier system for SV in bone regeneration applications.

  1. Liquid-phase pulsed laser ablation synthesis of graphitized carbon-encapsulated palladium core-shell nanospheres for catalytic reduction of nitrobenzene to aniline

    NASA Astrophysics Data System (ADS)

    Kim, Yu-jin; Ma, Rory; Reddy, D. Amaranatha; Kim, Tae Kyu

    2015-12-01

    Graphitized carbon-encapsulated palladium (Pd) core-shell nanospheres were produced via pulsed laser ablation of a solid Pd foil target submerged in acetonitrile. The microstructural features and optical properties of these nanospheres were characterized via high resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and UV-visible spectroscopy. Microstructural analysis indicated that the core-shell nanostructures consisted of single-crystalline cubic metallic Pd spheres that serve as the core material, over which graphitized carbon was anchored as a heterogeneous shell. The absorbance spectrum of the synthesized nanostructures exhibited a broad (absorption) band at ∼264 nm; this band corresponded to the typical inter-band transition of a metallic system and resulted possibly from the absorbance of the ionic Pd2+. The catalytic properties of the Pd and Pd@C core-shell nanostructures were investigated using the reduction of nitrobenzene to aniline by an excess amount of NaBH4 in an aqueous solution at room temperature, as a model reaction. Owing to the graphitized carbon-layered structure and the high specific surface area, the resulting Pd@C nanostructures exhibited higher conversion efficiencies than their bare Pd counterparts. In fact, the layered structure provided access to the surface of the Pd nanostructures for the hydrogenation reaction, owing to the synergistic effect between graphitized carbon and the nanostructures. Their unique structure and excellent catalytic performance render Pd@C core-shell nanostructures highly promising candidates for catalysis applications.

  2. Integration of living cells into nanostructures using non-conventional self-assembly

    NASA Astrophysics Data System (ADS)

    Carnes, Eric C.

    Patternable cell immobilization is an essential feature of any solid-state device designed for interrogating or exploiting living cells. Immobilized cells must remain viable in a robust matrix that promotes fluidic connectivity between the cells and their environment while retaining the ability to establish and maintain necessary chemical gradients. A suitable inorganic matrix can be constructed via evaporation-induced self-assembly of nanostructured silica, in which phospholipids are used in place of traditional surfactant structure-directing agents in order to enhance cell viability and to create a coherent interface between the cell and the surrounding three-dimensional nanostructure. We have used this technique to develop two distinct cell encapsulation processes: cell-directed assembly and cell-directed integration. Cell-directed assembly is a one-step procedure that provides superior viability of immobilized cells by encouraging cells to interact with the developing host matrix. Limitations of this system include low viability for some cell types due to exposure to solvents and stresses, as well as a lack of control over the developing host nanostructure. Cell-directed integration addresses these shortcomings by introducing a two-step process in which cells become encapsulated in a pre-formed silica matrix. The validity of each encapsulation method has been demonstrated with Gram-positive and Gram-negative bacteria, yeast, and mammalian cells. The ability of the immobilized cells to establish relevant gradients of ions or signaling molecules, a key feature of these systems, has been characterized. Additionally, extension of cell encapsulation to address lingering questions in cell biology is addressed. We have also adapted these immobilization processes to be compatible with a variety of patterning strategies having tailorable properties. Widely available photolithography techniques, as well as direct aerosol deposition, have been adapted to provide methods for obtaining both positive and negative transfer of desired cell patterns. Multi-step lithography is also used to create a highly functional system allowing spatial control of not only cells but also media and other molecules of interest.

  3. Nanofibers of fullerene C60 through interplay of ball-and-socket supermolecules.

    PubMed

    Hubble, Lee J; Raston, Colin L

    2007-01-01

    Mixing solutions of p-tBu-calix[5]arene and C(60) in toluene results in a 1:1 complex (C(60)) intersection(p-tBu-calix[5]arene), which precipitates as nanofibers. The principle structural unit is based on a host-guest ball-and-socket nanostructure of the two components, with an extended structure comprising zigzag/helical arrays of fullerenes (powder X-ray diffraction data coupled with molecular modeling). Under argon at temperatures above 309 degrees C, the fibers undergo selective volatilization of the calixarenes to afford C(60)-core nanostructures encapsulated in a graphitic material sheath, which exhibits a dramatic increase in surface area. Above 650 degrees C the material exhibits an ohmic conductance response, due to the encapsulation process.

  4. A biotemplated nickel nanostructure: Synthesis, characterization and antibacterial activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ashtari, Khadijeh; Fasihi, Javad; Mollania, Nasrin

    Highlights: • Nickel nanostructure-encapsulated bacteria were prepared using electroless deposition. • Bacterium surface was activated by red-ox reaction of its surface amino acids. • Interfacial changes at cell surfaces were investigated using fluorescence spectroscopy. • TEM and AFM depicted morphological changes. • Antibacterial activity of nanostructure was examined against different bacteria strains. - Abstract: Nickel nanostructure-encapsulated bacteria were prepared using the electroless deposition procedure and activation of bacterium cell surface by red-ox reaction of surface amino acids. The electroless deposition step occurred in the presence of Ni(II) and dimethyl amine boran (DMAB). Interfacial changes at bacteria cell surfaces during themore » coating process were investigated using fluorescence spectroscopy. Fluorescence of tryptophan residues was completely quenched after the deposition of nickel onto bacteria surfaces. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) depicted morphological changes on the surface of the bacterium. It was found that the Ni coated nanostructure was mechanically stable after ultrasonication for 20 min. Significant increase in surface roughness of bacteria was also observed after deposition of Ni clusters. The amount of coated Ni on the bacteria surface was calculated as 36% w/w. The antibacterial activity of fabricated nanostructure in culture media was examined against three different bacteria strains; Escherichia coli, Bacillus subtilis and Xantomonas campestris. The minimum inhibitory concentrations (MIC) were determined as 500 mg/L, 350 mg/L and 200 mg/L against bacteria, respectively.« less

  5. Treatment of Francisella infections via PLGA- and lipid-based nanoparticle delivery of antibiotics in a zebrafish model.

    PubMed

    Ulanova, Lilia S; Pinheiro, Marina; Vibe, Carina; Nunes, Claudia; Misaghian, Dorna; Wilson, Steven; Zhu, Kaizheng; Fenaroli, Federico; Winther-Larsen, Hanne C; Reis, Salette; Griffiths, Gareth

    2017-06-19

    We tested the efficiency of 2 different antibiotics, rifampicin and oxolinic acid, against an established infection caused by fish pathogen Francisella noatunensis ssp. orientalis (F.n.o.) in zebrafish. The drugs were tested in the free form as well as encapsulated into biodegradable nanoparticles, either polylactic-co-glycolic acid (PLGA) nanoparticles or nanostructured lipid carriers. The most promising therapies were PLGA-rifampicin nanoparticles and free oxolinic acid; the PLGA nanoparticles significantly delayed embryo mortality while free oxolinic acid prevented it. Encapsulation of rifampicin in both PLGA and nanostructured lipid carriers enhanced its efficiency against F.n.o. infection relative to the free drug. We propose that the zebrafish model is a robust, rapid system for initial testing of different treatments of bacterial diseases important for aquaculture.

  6. Synthesis of Graphite Encapsulated Metal Nanoparticles and Metal Catalyzed Nanotubes

    NASA Technical Reports Server (NTRS)

    vanderWal, R. L.; Dravid, V. P.

    1999-01-01

    This work focuses on the growth and inception of graphite encapsulated metal nanoparticles and metal catalyzed nanotubes using combustion chemistry. Deciphering the inception and growth mechanism(s) for these unique nanostructures is essential for purposeful synthesis. Detailed knowledge of these mechanism(s) may yield insights into alternative synthesis pathways or provide data on unfavorable conditions. Production of these materials is highly desirable given many promising technological applications.

  7. Marine structure derived calcium phosphate-polymer biocomposites for local antibiotic delivery.

    PubMed

    Macha, Innocent J; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L; Milthorpe, Bruce

    2015-01-20

    Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery.

  8. Marine Structure Derived Calcium Phosphate–Polymer Biocomposites for Local Antibiotic Delivery

    PubMed Central

    Macha, Innocent J.; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L.; Milthorpe, Bruce

    2015-01-01

    Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery. PMID:25608725

  9. Effect of Lipid-Based Nanostructure on Protein Encapsulation within the Membrane Bilayer Mimetic Lipidic Cubic Phase Using Transmembrane and Lipo-proteins from the Beta-Barrel Assembly Machinery.

    PubMed

    van 't Hag, Leonie; Shen, Hsin-Hui; Lin, Tsung-Wu; Gras, Sally L; Drummond, Calum J; Conn, Charlotte E

    2016-11-29

    A fundamental understanding of the effect of amphiphilic protein encapsulation on the nanostructure of the bicontinuous cubic phase is crucial to progressing biomedical and biological applications of these hybrid protein-lipid materials, including as drug delivery vehicles, as biosensors, biofuel cells and for in meso crystallization. The relationship between the lipid nanomaterial and the encapsulated protein, however, remains poorly understood. In this study, we investigated the effect of incorporating the five transmembrane and lipo-proteins which make up the β-barrel assembly machinery from Gram-negative bacteria within a series of bicontinuous cubic phases. The transmembrane β-barrel BamA caused an increase in lattice parameter of the cubic phase upon encapsulation. By contrast, the mainly hydrophilic lipo-proteins BamB-E caused the cubic phase lattice parameters to decrease, despite their large size relative to the diameter of the cubic phase water channels. Analysis of the primary amino acid sequence was used to rationalize this effect, based on specific interactions between aromatic amino acids within the proteins and the polar-apolar interface. Other factors that were found to have an effect were lateral bilayer pressure and rigidity within the lipid bilayer, water channel diameter, and size and structure of the lipo-proteins. The data presented suggest that hydrophilic bioactive molecules can be selectively encapsulated within the cubic phase by using a lipid anchor or aromatic amino acids, for drug delivery or biosensing applications.

  10. Facile and generalized encapsulations of inorganic nanocrystals with nitrogen-doped carbonaceous coating for multifunctionality

    NASA Astrophysics Data System (ADS)

    Yang, Yong; Zhang, Jingchao; Wang, Shitong; Xu, Xiaobin; Zhang, Zhicheng; Wang, Pengpeng; Tang, Zilong; Wang, Xun

    2015-02-01

    A simple strategy toward versatile encapsulations of inorganic nanocrystals, through a green hydrothermal treatment of commercial polyurethane sponge, was developed. This approach enables us to realize a general method to form a surface-adherent, N-doped coating with a controllable thickness for well-defined structures. These composites exhibit active properties in optical applications and energy storage. For example, N-doped carbon encapsulated Fe2O3 nanoboxes show a very high discharge capacity and outstanding cyclability, and the capacity still remained at 1086 mA h g-1 at a current density of 400 mA g-1 after 200 cycles. Our results described here provide a simple surface coating technique to design various functional nanostructures.A simple strategy toward versatile encapsulations of inorganic nanocrystals, through a green hydrothermal treatment of commercial polyurethane sponge, was developed. This approach enables us to realize a general method to form a surface-adherent, N-doped coating with a controllable thickness for well-defined structures. These composites exhibit active properties in optical applications and energy storage. For example, N-doped carbon encapsulated Fe2O3 nanoboxes show a very high discharge capacity and outstanding cyclability, and the capacity still remained at 1086 mA h g-1 at a current density of 400 mA g-1 after 200 cycles. Our results described here provide a simple surface coating technique to design various functional nanostructures. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07181f

  11. Synthesis of nanostructured materials in inverse miniemulsions and their applications.

    PubMed

    Cao, Zhihai; Ziener, Ulrich

    2013-11-07

    Polymeric nanogels, inorganic nanoparticles, and organic-inorganic hybrid nanoparticles can be prepared via the inverse miniemulsion technique. Hydrophilic functional cargos, such as proteins, DNA, and macromolecular fluoresceins, may be conveniently encapsulated in these nanostructured materials. In this review, the progress of inverse miniemulsions since 2000 is summarized on the basis of the types of reactions carried out in inverse miniemulsions, including conventional free radical polymerization, controlled/living radical polymerization, polycondensation, polyaddition, anionic polymerization, catalytic oxidation reaction, sol-gel process, and precipitation reaction of inorganic precursors. In addition, the applications of the nanostructured materials synthesized in inverse miniemulsions are also reviewed.

  12. Pd0@Polyoxometalate Nanostructures as Green Electrocatalysts: Illustrative Example of Hydrogen Production

    PubMed Central

    Biboum, Rosa N.; Keita, Bineta; Franger, Sylvain; Njiki, Charles P. Nanseu; Zhang, Guangjin; Zhang, Jie; Liu, Tianbo; Mbomekalle, Israel-Martyr; Nadjo, Louis

    2010-01-01

    Green-chemistry type procedures were used to synthesize Pd0 nanostructures encapsulated by a vanadium-substituted Wells-Dawson-type polyoxometalate (Pd0@POM). The cyclic voltammogram run with the Pd0@POM-modified glassy carbon electrode shows well-defined waves, associated with Pd0 nanostructures and the VV/VIV redox couple. The Pd0@POM-modified electrode displayed remarkably reproducible cyclic voltammetry patterns. The hydrogen evolution reaction (HER) was selected as an illustrative example to test the electrocatalytic behavior of the electrode. The kinetic parameters of the HER show the high efficiency of the Pd0@POM-modified electrode. This is the first example of electrochemical characterization of a modified electrode based on a vanado-tungstic POM and Pd0 nanostructures.

  13. Enzyme sensitive smart inulin-dehydropeptide conjugate self-assembles into nanostructures useful for targeted delivery of ornidazole.

    PubMed

    Shivhare, Kriti; Garg, Charu; Priyam, Ayushi; Gupta, Alka; Sharma, Ashwani Kumar; Kumar, Pradeep

    2018-01-01

    Molecular self-assembly of biodegradable amphiphilic polymers allows rational design of biocompatible nanomaterials for drug delivery. Use of substituted polysaccharides for such applications offers the ease of design and synthesis, and provides higher biofunctionality and biocompatibility to nanomaterials. The present work focuses on the synthesis, characterization and potential biomedical applications of self-assembled polysaccharide-based materials. We demonstrated that the synthesized amphiphilic inulin self-assembled in aqueous medium into nanostructures with average size in the range of 146-486nm and encapsulated hydrophobic therapeutic molecule, ornidazole. Hydrophophic dehydropeptide was conjugated with inulin via a biocompatible ester linkage. Dehydrophenylalanine, an unusual amino acid, was incorporated in the peptide to make it stable at a broader range of pH as well as against proteases. The resulting core-shell type of nanostructures could encapsulate ornidazole in the hydrophobic core and released it in a controlled fashion. By taking the advantage of inulin, which gets degraded in the colon by colonic bacteria, the effect of enzyme, inulinase, present in the microflora of the large intestine, on inulin-peptide degradation followed by drug release has been studied. Altogether, small peptide conjugated to inulin offers novel scaffold for the future design of nanostructures with potential applications in the field of targeted drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Crystalline silicon carbide nanoparticles encapsulated in branched wavelike carbon nanotubes: synthesis and optical properties.

    PubMed

    Xi, Guangcheng; Yu, Shijun; Zhang, Rui; Zhang, Meng; Ma, Dekun; Qian, Yitai

    2005-07-14

    A novel nanostructure, cubic silicon carbide (3C-SiC) nanoparticles encapsulated in branched wavelike carbon nanotubes have been prepared by a reaction of 1,2-dimenthoxyethane (CH3OCH2CH2OCH3), SiCl4, and Mg in an autoclave at 600 degrees C. According to X-ray powder diffraction, the products are composed of 3C-SiC and carbon. TEM and HRTEM images show that the as-synthesized products are composed of 3C-SiC nanoparticles encapsulated in branched carbon nanotubes with wavelike walls. The diameter of the 3C-SiC cores is approximately 20-40 nm and the thickness of the carbon shells is about 3-5 nm. In Raman scattering spectroscopy, both the TO (Gamma) phonon line and the LO (Gamma) phonon line have red shifts about 6 cm(-1) relative to that for the bulk 3C-SiC. The photoluminescence (PL) spectrum shows that there are two emission peaks: blue light emission (431 nm) and violet light emission (414 nm). A sequential deposition growth process (with cores as the templates for the shells) for the nanostructure was proposed.

  15. Nanostructured lipid carriers: effect of solid phase fraction and distribution on the release of encapsulated materials.

    PubMed

    Dan, Nily

    2014-11-25

    Emulsions, solid lipid nanoparticles (SLN), and nanostructured lipid carriers (NLC) containing a mix of liquid and solid domains are of interest as encapsulation vehicles for hydrophobic compounds. Studies of the release rate from these particles yield contradictory results: Some find that increasing the fraction of solid phase increases the rate of release and others the opposite. In this paper we study the release of encapsulated materials from lipid-based nanoparticles using Monte Carlo simulations. We find that, quite surprisingly, the release rate is largely insensitive to the size of solid domains or the fraction of solid phase. However, the distribution of the domains significantly affects the rate of release: Solid domains located at the interface with the surrounding solution inhibit transport, while nanoparticles where the solid domains are concentrated in the center enhance it. The latter can lead to release rates in NLCs that are faster than in the equivalent emulsions. We conclude that controlling the release rate from NLCs requires the ability to determine the location and distribution of the solid phase, which may be achieved through choice of the surfactants stabilizing the particles, incorporation of nucleation sites, and/or the cooling rates and temperatures.

  16. Nanostructures for protein drug delivery.

    PubMed

    Pachioni-Vasconcelos, Juliana de Almeida; Lopes, André Moreni; Apolinário, Alexsandra Conceição; Valenzuela-Oses, Johanna Karina; Costa, Juliana Souza Ribeiro; Nascimento, Laura de Oliveira; Pessoa, Adalberto; Barbosa, Leandro Ramos Souza; Rangel-Yagui, Carlota de Oliveira

    2016-02-01

    Use of nanoscale devices as carriers for drugs and imaging agents has been extensively investigated and successful examples can already be found in therapy. In parallel, recombinant DNA technology together with molecular biology has opened up numerous possibilities for the large-scale production of many proteins of pharmaceutical interest, reflecting in the exponentially growing number of drugs of biotechnological origin. When we consider protein drugs, however, there are specific criteria to take into account to select adequate nanostructured systems as drug carriers. In this review, we highlight the main features, advantages, drawbacks and recent developments of nanostructures for protein encapsulation, such as nanoemulsions, liposomes, polymersomes, single-protein nanocapsules and hydrogel nanoparticles. We also discuss the importance of nanoparticle stabilization, as well as future opportunities and challenges in nanostructures for protein drug delivery.

  17. Low temperature oxidation synthesis of carbon encapsulated Cr2O3 nanocrystals and its lithium storage performance

    NASA Astrophysics Data System (ADS)

    Zhou, Yun; Liu, Boyang; Shao, Yingfeng; Fan, Chunhua; Fan, Runhua; Wen, Bosheng

    A highly efficient and convenient strategy is developed for the one-step in-situ synthesis of carbon encapsulated Cr2O3 nanocrystals with core-shell structure (Cr2O3@C). The explosive reaction of chromocene with ammonium persulfate in an autoclave at 200∘C is crucial for the formation of this nanostructure. The Cr2O3 nanocrystals have a diameter of 5 to 20nm, which are entirely encapsulated by the amorphous carbon shell. The Cr2O3@C anode can retain a stable reversible capacity of 397mAhg-1 after 50 cycles at a current density of 119mA g-1.

  18. Magnetic properties and transmission electron microscopy studies of Ni nanoparticles encapsulated in carbon nanocages and carbon nanotubes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    He Chunnian; Zhao Naiqin; Shi Chunsheng

    2008-08-04

    Three types of carbon nanomaterials, including bamboo-shaped carbon nanotubes with Ni encapsulated and hollow and Ni catalytic particles filled carbon nanocages, have been prepared by methane catalytic decomposition at a relatively low temperature. Transmission electron microscopy observations showed that fascinating fullerene-like Ni-C (graphitic) core-shell nanostructures predominated. Detailed examination of high-resolution transmission electron microscopy showed that the walls of bamboo-shaped carbon nanotubes with quasi-cone catalytic particles encapsulated consisted of oblique graphene planes with respect to the tube axis. The Ni particles encapsulated in the carbon nanocages were larger than that encapsulated in carbon nanotubes, but the diameters of the cores ofmore » hollow carbon nanocages were less than that of Ni particles encapsulated in carbon nanotubes, suggesting that the sizes of catalyst particles played an important role during carbon nanomaterial growth. The magnetic properties of the carbon nanomaterials were measured, which showed relatively large coercive force (H{sub c} = 138.4 O{sub e}) and good ferromagnetism (M{sub r}/M{sub s} = 0.325)« less

  19. Confined-Volume Effect on the Thermal Properties of Encapsulated Phase Change Materials for Thermal Energy Storage.

    PubMed

    De Castro, Paula F; Ahmed, Adham; Shchukin, Dmitry G

    2016-03-18

    We have encapsulated the heat exchange material, n-docosane, into polyurethane capsules of different sizes. Decreasing the size of the capsules leads to changes of the crystallinity of phase-change material as well as melting/crystallization temperature. The novelty of the paper includes 1) protection of the nanostructured energy-enriched materials against environment during storage and controlled release of the encapsulated energy on demand and 2) study of the structure and surface-to-volume properties of the energy-enriched materials dispersed in capsules of different sizes. The stability of energy nanomaterials, influence of capsule diameter on their energy capacity, homogeneity and operation lifetime are investigated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Fetoprotein Derived Short Peptide Coated Nanostructured Amphiphilic Surfaces for Targeting Mouse Breast Cancer Cells

    NASA Astrophysics Data System (ADS)

    Brown, Alexandra M.; Miranda-Alarćon, Yoliem S.; Knoll, Grant A.; Santora, Anthony M.; Banerjee, Ipsita A.

    In this work, self-assembled tumor targeting nanostructured surfaces were developed from a newly designed amphiphile by conjugating boc protected isoleucine with 2,2‧ ethylenedioxy bis ethylamine (IED). To target mouse mammary tumor cells, a short peptide sequence derived from the human alpha-fetoprotein (AFP), LSEDKLLACGEG was attached to the self-assembled nanostructures. Tumor targeting and cell proliferation were examined in the presence of nanoscale assemblies. To further obliterate mouse breast tumor cells, the chemotherapeutic drug tamoxifen was then entrapped into the nanoassemblies. Our studies indicated that the targeting systems were able to efficiently encapsulate and release tamoxifen. Cell proliferation studies showed that IED-AFP peptide loaded with tamoxifen decreased the proliferation of breast cancer cells while in the presence of the IED-AFP peptide nanoassemblies alone, the growth was relatively slower. In the presence of human dermal fibroblasts however cell proliferation continued similar to controls. Furthermore, the nanoscale assemblies were found to induce apoptosis in mouse breast cancer cells. To examine live binding interactions, SPR analysis revealed that tamoxifen encapsulated IED-AFP peptide nanoassemblies bound to the breast cancer cells more efficiently compared to unencapsulated assemblies. Thus, we have developed nanoscale assemblies that can specifically bind to and target tumor cells, with increased toxicity in the presence of a chemotherapeutic drug.

  1. Nanoscale High Energetic Materials: A Polymeric Nitrogen Chain N8 Confined inside a Carbon Nanotube

    NASA Astrophysics Data System (ADS)

    Abou-Rachid, Hakima; Hu, Anguang; Timoshevskii, Vladimir; Song, Yanfeng; Lussier, Louis-Simon

    2008-05-01

    We present a theoretical study of a new hybrid material, nanostructured polymeric nitrogen, where a polymeric nitrogen chain is encapsulated in a carbon nanotube. The electronic and structural properties of the new system are studied by means of ab initio electronic structure and molecular dynamics calculations. Finite temperature simulations demonstrate the stability of this nitrogen phase at ambient pressure and room temperature using carbon nanotube confinement. This nanostructured confinement may open a new path towards stabilizing polynitrogen or polymeric nitrogen at ambient conditions.

  2. Copper nanowire-graphene core-shell nanostructure for highly stable transparent conducting electrodes.

    PubMed

    Ahn, Yumi; Jeong, Youngjun; Lee, Donghwa; Lee, Youngu

    2015-03-24

    A copper nanowire-graphene (CuNW-G) core-shell nanostructure was successfully synthesized using a low-temperature plasma-enhanced chemical vapor deposition process at temperatures as low as 400 °C for the first time. The CuNW-G core-shell nanostructure was systematically characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Raman, and X-ray photoelectron spectroscopy measurements. A transparent conducting electrode (TCE) based on the CuNW-G core-shell nanostructure exhibited excellent optical and electrical properties compared to a conventional indium tin oxide TCE. Moreover, it showed remarkable thermal oxidation and chemical stability because of the tight encapsulation of the CuNW with gas-impermeable graphene shells. The potential suitability of CuNW-G TCE was demonstrated by fabricating bulk heterojunction polymer solar cells. We anticipate that the CuNW-G core-shell nanostructure can be used as an alternative to conventional TCE materials for emerging optoelectronic devices such as flexible solar cells, displays, and touch panels.

  3. In Vivo Deep Tissue Fluorescence and Magnetic Imaging Employing Hybrid Nanostructures.

    PubMed

    Ortgies, Dirk H; de la Cueva, Leonor; Del Rosal, Blanca; Sanz-Rodríguez, Francisco; Fernández, Nuria; Iglesias-de la Cruz, M Carmen; Salas, Gorka; Cabrera, David; Teran, Francisco J; Jaque, Daniel; Martín Rodríguez, Emma

    2016-01-20

    Breakthroughs in nanotechnology have made it possible to integrate different nanoparticles in one single hybrid nanostructure (HNS), constituting multifunctional nanosized sensors, carriers, and probes with great potential in the life sciences. In addition, such nanostructures could also offer therapeutic capabilities to achieve a wider variety of multifunctionalities. In this work, the encapsulation of both magnetic and infrared emitting nanoparticles into a polymeric matrix leads to a magnetic-fluorescent HNS with multimodal magnetic-fluorescent imaging abilities. The magnetic-fluorescent HNS are capable of simultaneous magnetic resonance imaging and deep tissue infrared fluorescence imaging, overcoming the tissue penetration limits of classical visible-light based optical imaging as reported here in living mice. Additionally, their applicability for magnetic heating in potential hyperthermia treatments is assessed.

  4. Synthesis on structure and properties of zinc nanocrystal in high ordered 3D nanostructures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sathyaseelan, B., E-mail: bsseelan03@gmail.com; Manigandan, A.; Anbarasu, V.

    2015-06-24

    The wet impregnation method was employed to prepare ZnO encapsulated in mesoporous silica (ZnO/KIT-6). The prepared ZnO/KIT-6 samples have been studied by X-ray diffraction, transmission electron microscope, and nitrogen adsorption–desorption isotherm. The low angle powder XRD patterns of Calcined ZnO/KIT-6 materials showed a phase that can be indexed to cubic Ia3d. Tem images revealed well ordered cubic 3D nanoporous chennels. The ZnO encapsulated in KIT-6 can be used as light-emitting diodes and ultraviolet nanolasers.

  5. PET/NIRF/MRI triple functional iron oxide nanoparticles.

    PubMed

    Xie, Jin; Chen, Kai; Huang, Jing; Lee, Seulki; Wang, Jinhua; Gao, Jinhao; Li, Xingguo; Chen, Xiaoyuan

    2010-04-01

    Engineered nanoparticles with theranostic functions have attracted a lot of attention for their potential role in the dawning era of personalized medicine. Iron oxide nanoparticles (IONPs), with their advantages of being non-toxic, biodegradable and inexpensive, are candidate platforms for the buildup of theranostic nanostructures; however, progress in using them has been limited largely due to inefficient drug loading and delivery. In the current study, we utilized dopamine to modify the surface of IONPs, yielding nanoconjugates that can be easily encapsulated into human serum albumin (HSA) matrices (clinically utilized drug carriers). This nanosystem is well-suited for dual encapsulation of IONPs and drug molecules, because the encapsulation is achieved in a way that is similar to common drug loading. To assess the biophysical characteristics of this novel nanosystem, the HSA coated IONPs (HSA-IONPs) were dually labeled with (64)Cu-DOTA and Cy5.5, and tested in a subcutaneous U87MG xenograft mouse model. In vivo positron emission tomography (PET)/near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) tri-modality imaging, and ex vivo analyses and histological examinations were carefully conducted to investigate the in vivo behavior of the nanostructures. With the compact HSA coating, the HSA-IONPs manifested a prolonged circulation half-life; more impressively, they showed massive accumulation in lesions, high extravasation rate, and low uptake of the particles by macrophages at the tumor area. Published by Elsevier Ltd.

  6. Development of nanostructured lipid carrier for dacarbazine delivery

    NASA Astrophysics Data System (ADS)

    Almousallam, Musallam; Moia, Claudia; Zhu, Huijun

    2015-09-01

    Dacarbazine (Dac) is one of the most commonly used chemotherapy drugs for treating various cancers. However, its poor water solubility, short half-life in blood circulation, low response rate and high side effect limit its application. This study aimed to improve the drug solubility and prolong drug release by developing nanostructured lipid carriers (NLCs) for Dac delivery. The NLC and Dac-encapsulated NLC were synthesized with precirol ATO 5 and isopropyl myristate as lipids, tocopheryl polyethylene glycol succinate, soybean lecithin and Kolliphor P 188 as co-surfactants. The NLCs with controlled size were achieved using high shear dispersion following solidification of oil-in-water emulsion. For Dac encapsulation, the smallest NLC with 155 ± 10 nm in size, 0.2 ± 0.01 polydispersion index and -43.4 ± 2 mV zeta potential was selected. The resultant DLC-Dac possessed size, polydispersion index and zeta potential of 190 ± 10, 0.2 ± 0.01, and -43.5 ± 1.2, respectively. The drug encapsulation efficiency and drug loading were 98.5 % and 14 %, respectively. In vitro drug release study showed a biphasic pattern, with 50 % released in the first 2 h, and the remaining released sustainably for up to 30 h. This is the first report on the development of NLC for Dac delivery, implying that NLC could be a new potential candidate as drug carrier to improve the therapeutic profile of Dac.

  7. Cytotoxicity of solid lipid nanoparticles and nanostructured lipid carriers containing the local anesthetic dibucaine designed for topical application

    NASA Astrophysics Data System (ADS)

    Barbosa, R. M.; da Silva, C. M. G.; Bella, T. S.; de Araújo, D. R.; Marcato, P. D.; Durán, N.; de Paula, E.

    2013-04-01

    Dibucaine (DBC) is powerful long-lasting local anesthetic, but it is also considered fairly toxic to the CNS. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have attracted attention as carriers for drug delivery. The aim of this study was to develop and to evaluate the cytotoxic activity of DBC-loaded SLN and NLC against 3T3 fibroblast and HaCat keratinocyte cells. The SLN and NLC had myristyl myristate and Liponate®GC as their lipid matrices, respectively, plus a surfactant. SLN and NLC were characterized in terms in their diameter, size distribution, surface charge and DBC encapsulation efficiency. The particle size of SLN and NLC were around 234.33 and 166.62 nm, respectively. The polydispersity index was kept below 0.2 for both nanomaterials. Negative surface charges were observed for both nanoparticles, which decreased in the presence of the anesthetic. Encapsulation efficiency reached 76% and 90%, respectively, in SLN and NLC. DBC alone was found to be toxic to 3T3 and HaCat cells in culture. However, NLC and SLN loaded DBC decreased its intrinsic cytotoxic effect against 3T3 and HaCat cells. In conclusion, encapsulation of DBC in SLN and NLC decreased the in vitro toxicity of the local anesthetic, indicating the potential of these nanocarriers for clinical applications.

  8. Direct writing of metal nanostructures: lithographic tools for nanoplasmonics research.

    PubMed

    Leggett, Graham J

    2011-03-22

    Continued progress in the fast-growing field of nanoplasmonics will require the development of new methods for the fabrication of metal nanostructures. Optical lithography provides a continually expanding tool box. Two-photon processes, as demonstrated by Shukla et al. (doi: 10.1021/nn103015g), enable the fabrication of gold nanostructures encapsulated in dielectric material in a simple, direct process and offer the prospect of three-dimensional fabrication. At higher resolution, scanning probe techniques enable nanoparticle particle placement by localized oxidation, and near-field sintering of nanoparticulate films enables direct writing of nanowires. Direct laser "printing" of single gold nanoparticles offers a remarkable capability for the controlled fabrication of model structures for fundamental studies, particle-by-particle. Optical methods continue to provide a powerful support for research into metamaterials.

  9. Enhanced Ethanol Gas Sensing Properties of SnO2-Core/ZnO-Shell Nanostructures

    PubMed Central

    Tharsika, T.; Haseeb, A. S. M. A.; Akbar, Sheikh A.; Sabri, Mohd Faizul Mohd; Hoong, Wong Yew

    2014-01-01

    An inexpensive single-step carbon-assisted thermal evaporation method for the growth of SnO2-core/ZnO-shell nanostructures is described, and the ethanol sensing properties are presented. The structure and phases of the grown nanostructures are investigated by field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) techniques. XRD analysis indicates that the core-shell nanostructures have good crystallinity. At a lower growth duration of 15 min, only SnO2 nanowires with a rectangular cross-section are observed, while the ZnO shell is observed when the growth time is increased to 30 min. Core-shell hierarchical nanostructures are present for a growth time exceeding 60 min. The growth mechanism for SnO2-core/ZnO-shell nanowires and hierarchical nanostructures are also discussed. The sensitivity of the synthesized SnO2-core/ZnO-shell nanostructures towards ethanol sensing is investigated. Results show that the SnO2-core/ZnO-shell nanostructures deposited at 90 min exhibit enhanced sensitivity to ethanol. The sensitivity of SnO2-core/ZnO-shell nanostructures towards 20 ppm ethanol gas at 400 °C is about ∼5-times that of SnO2 nanowires. This improvement in ethanol gas response is attributed to high active sensing sites and the synergistic effect of the encapsulation of SnO2 by ZnO nanostructures. PMID:25116903

  10. Nanostructured Lipid Carriers Loaded with Baicalin: An Efficient Carrier for Enhanced Antidiabetic Effects

    PubMed Central

    Shi, Feng; Wei, Zheng; Zhao, Yingying; Xu, Ximing

    2016-01-01

    Context: Recent studies have demonstrated that baicalin has antihyperglycemic effects by inhibiting lipid peroxidation. Baicalin is low hydrophilic and poorly absorbed after oral administration. Thus, a suitable formulation is highly desired to overcome the disadvantages of baicalin. Objective: The objective of this work was to prepare baicalin-loaded nanostructured lipid carriers (B-NLCs) for enhanced antidiabetic effects. Materials and Methods: B-NLCs were prepared by high-pressure homogenization method using Precirol as the solid lipid and Miglyol as the liquid lipid. The properties of the NLCs, such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE), were investigated. The morphology of NLCs was observed by transmission electron microscopy. In addition, drug release and antidiabetic activity were also studied. Results: The results revealed that B-NLCs particles were uniformly in the nanosize range and of spherical morphology with a mean size of 92 ± 3.1 nm, a ZP of −31.35 ± 3.08 mV, and an EE of 85.29 ± 3.42%. Baicalin was released from NLCs in a sustained manner. In addition, B-NLCs showed a significantly higher antidiabetic efficacy compared with baicalin. Conclusion: B-NLCs described in this study are well-suited for the delivery of baicalin. SUMMARY Currently, herbal medicines have attracted increasing attention as a complementary approach for type 2 diabetesBaicalin has antihyperglycemic effects by inhibiting lipid peroxidationA suitable formulation is highly desired to overcome the disadvantages (poor solubility and low bioavailability) of baicalinNanostructured lipid carriers could enhance the antidiabetic effects of baicalin. Abbreviations used: B-NLCs: Baicalin-Loaded Nanostructured Lipid Carriers, B-SUS: Baicalin Water Suspension, EE: Encapsulation Efficiency, FBG: Fasting Blood Glucose, HbAlc: Glycosylated Hemoglobin, HPLC: High-performance Liquid Chromatography; NLCs: Nanostructured Lipid Carriers, PI: Polydispersity Index, SD: Sprague-Dawley, SLNs: Solid lipid nanoparticles, STZ: Streptozotocin, TC: Total cholesterol, TEM: Transmission Electron Microscope, TG: Total Triglyceride, ZP: Zeta Potential. PMID:27601850

  11. Nanostructured Lipid Carriers Loaded with Baicalin: An Efficient Carrier for Enhanced Antidiabetic Effects.

    PubMed

    Shi, Feng; Wei, Zheng; Zhao, Yingying; Xu, Ximing

    2016-01-01

    Recent studies have demonstrated that baicalin has antihyperglycemic effects by inhibiting lipid peroxidation. Baicalin is low hydrophilic and poorly absorbed after oral administration. Thus, a suitable formulation is highly desired to overcome the disadvantages of baicalin. The objective of this work was to prepare baicalin-loaded nanostructured lipid carriers (B-NLCs) for enhanced antidiabetic effects. B-NLCs were prepared by high-pressure homogenization method using Precirol as the solid lipid and Miglyol as the liquid lipid. The properties of the NLCs, such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE), were investigated. The morphology of NLCs was observed by transmission electron microscopy. In addition, drug release and antidiabetic activity were also studied. The results revealed that B-NLCs particles were uniformly in the nanosize range and of spherical morphology with a mean size of 92 ± 3.1 nm, a ZP of -31.35 ± 3.08 mV, and an EE of 85.29 ± 3.42%. Baicalin was released from NLCs in a sustained manner. In addition, B-NLCs showed a significantly higher antidiabetic efficacy compared with baicalin. B-NLCs described in this study are well-suited for the delivery of baicalin. Currently, herbal medicines have attracted increasing attention as a complementary approach for type 2 diabetesBaicalin has antihyperglycemic effects by inhibiting lipid peroxidationA suitable formulation is highly desired to overcome the disadvantages (poor solubility and low bioavailability) of baicalinNanostructured lipid carriers could enhance the antidiabetic effects of baicalin. Abbreviations used: B-NLCs: Baicalin-Loaded Nanostructured Lipid Carriers, B-SUS: Baicalin Water Suspension, EE: Encapsulation Efficiency, FBG: Fasting Blood Glucose, HbAlc: Glycosylated Hemoglobin, HPLC: High-performance Liquid Chromatography; NLCs: Nanostructured Lipid Carriers, PI: Polydispersity Index, SD: Sprague-Dawley, SLNs: Solid lipid nanoparticles, STZ: Streptozotocin, TC: Total cholesterol, TEM: Transmission Electron Microscope, TG: Total Triglyceride, ZP: Zeta Potential.

  12. Camphor-mediated synthesis of carbon nanoparticles, graphitic shell encapsulated carbon nanocubes and carbon dots for bioimaging

    PubMed Central

    Oza, Goldie; Ravichandran, M.; Merupo, Victor-Ishrayelu; Shinde, Sachin; Mewada, Ashmi; Ramirez, Jose Tapia; Velumani, S.; Sharon, Madhuri; Sharon, Maheshwar

    2016-01-01

    A green method for an efficient synthesis of water-soluble carbon nanoparticles (CNPs), graphitic shell encapsulated carbon nanocubes (CNCs), Carbon dots (CDs) using Camphor (Cinnamomum camphora) is demonstrated. Here, we describe a competent molecular fusion and fission route for step-wise synthesis of CDs. Camphor on acidification and carbonization forms CNPs, which on alkaline hydrolysis form CNCs that are encapsulated by thick graphitic layers and on further reduction by sodium borohydride yielded CDs. Though excitation wavelength dependent photoluminescence is observed in all the three carbon nanostructures, CDs possess enhanced photoluminescent properties due to more defective carbonaceous structures. The surface hydroxyl and carboxyl functional groups make them water soluble in nature. They possess excellent photostability, higher quantum yield, increased absorption, decreased cytotoxicity and hence can be utilized as a proficient bio imaging agent. PMID:26905737

  13. Camphor-mediated synthesis of carbon nanoparticles, graphitic shell encapsulated carbon nanocubes and carbon dots for bioimaging

    NASA Astrophysics Data System (ADS)

    Oza, Goldie; Ravichandran, M.; Merupo, Victor-Ishrayelu; Shinde, Sachin; Mewada, Ashmi; Ramirez, Jose Tapia; Velumani, S.; Sharon, Madhuri; Sharon, Maheshwar

    2016-02-01

    A green method for an efficient synthesis of water-soluble carbon nanoparticles (CNPs), graphitic shell encapsulated carbon nanocubes (CNCs), Carbon dots (CDs) using Camphor (Cinnamomum camphora) is demonstrated. Here, we describe a competent molecular fusion and fission route for step-wise synthesis of CDs. Camphor on acidification and carbonization forms CNPs, which on alkaline hydrolysis form CNCs that are encapsulated by thick graphitic layers and on further reduction by sodium borohydride yielded CDs. Though excitation wavelength dependent photoluminescence is observed in all the three carbon nanostructures, CDs possess enhanced photoluminescent properties due to more defective carbonaceous structures. The surface hydroxyl and carboxyl functional groups make them water soluble in nature. They possess excellent photostability, higher quantum yield, increased absorption, decreased cytotoxicity and hence can be utilized as a proficient bio imaging agent.

  14. Catalysis by Nanostructures: Methane, Ethylene Oxide, and Propylene Oxide Synthesis on Ag, Cu or Au Nanoclusters

    DTIC Science & Technology

    2008-02-07

    22 nm) were prepared by reducing a Au salt, and encapsulating the Au nanoparticles formed in a polymer33 . A variety of high area oxides (TiO 2, ZnO ...Morphologies Utilizing a Combinatorial Electrochemistry Methodology. Ph. D. dissertation, Chemical Engineering, University of California, Santa Barbara (2004

  15. Nanostructured polysaccharidic microcapsules for intracellular release of cisplatin.

    PubMed

    Vergaro, Viviana; Papadia, Paride; Petrini, Paola; Fanizzi, Francesco Paolo; De Pascali, Sandra A; Baldassarre, Francesca; Pastorino, Laura; Ciccarella, Giuseppe

    2017-06-01

    Carbohydrate polimeric microcapsules were assembled using a LbL approach onto a CaCO 3 core. The microcapsules were used to delivery the anticancer drug cisplatin into HeLa and MCF-7 cancer cell lines. Drug encapsulation, measured by ICP spectroscopy, was around 50% of the charging solution. Fluorimetric measurements showed an efficient cellular uptake of polysacchardic microcapsules in both cell lines. The drug-loaded capsules demonstrated a better efficiency against cell viability than the free drug. Specifically, the amount of platinum reaching genomic DNA was measured, showing that encapsulation improves the nuclear delivery of the drug for both cell lines. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Water-Dispersible, Multifunctional, Magnetic, Luminescent Silica-Encapsulated Composite Nanotubes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sutter, E.; Wong, S.; Zhou, H.

    2010-02-05

    A multifunctional one-dimensional nanostructure incorporating both CdSe quantum dots (QDs) and Fe{sub 3}O{sub 4} nanoparticles (NPs) within a SiO{sub 2}-nanotube matrix is successfully synthesized based on the self-assembly of preformed functional NPs, allowing for control over the size and amount of NPs contained within the composite nanostructures. This specific nanostructure is distinctive because both the favorable photoluminescent and magnetic properties of QD and NP building blocks are incorporated and retained within the final silica-based composite, thus rendering it susceptible to both magnetic guidance and optical tracking. Moreover, the resulting hydrophilic nanocomposites are found to easily enter into the interiors ofmore » HeLa cells without damage, thereby highlighting their capability not only as fluorescent probes but also as possible drug-delivery vehicles of interest in nanobiotechnology.« less

  17. Three-Dimensional Encapsulation of Saccharomyces cerevisiae in Silicate Matrices Creates Distinct Metabolic States as Revealed by Gene Chip Analysis.

    PubMed

    Fazal, Zeeshan; Pelowitz, Jennifer; Johnson, Patrick E; Harper, Jason C; Brinker, C Jeffrey; Jakobsson, Eric

    2017-04-25

    In order to design hybrid cellular/synthetic devices such as sensors and vaccines, it is important to understand how the metabolic state of living cells changes upon physical confinement within three-dimensional (3D) matrices. We analyze the gene expression patterns of stationary phase Saccharomyces cerevisiae (S. cerevisiae) cells encapsulated within three distinct nanostructured silica matrices and relate those patterns to known naturally occurring metabolic states. Silica encapsulation methods employed were lipid-templated mesophase silica thin films formed by cell-directed assembly (CDA), lipid-templated mesophase silica particles formed by spray drying (SD), and glycerol-doped silica gel monoliths prepared from an aqueous silicate (AqS+g) precursor solution. It was found that the cells for all three-encapsulated methods enter quiescent states characteristic of response to stress, albeit to different degrees and with differences in detail. By the measure of enrichment of stress-related gene ontology categories, we find that the AqS+g encapsulation is more amenable to the cells than CDA and SD encapsulation. We hypothesize that this differential response in the AqS+g encapsulation is related to four properties of the encapsulating gel: (1) oxygen permeability, (2) relative softness of the material, (3) development of a protective sheath around individual cells (visible in TEM micrographs vide infra), and (4) the presence of glycerol in the gel, which has been previously noted to serve as a protectant for encapsulated cells and can serve as the sole carbon source for S. cerevisiae under aerobic conditions. This work represents a combination of experiment and analysis aimed at the design and development of 3D encapsulation procedures to induce, and perhaps control, well-defined physiological behaviors.

  18. Enhanced skin penetration of lidocaine through encapsulation into nanoethosomes and nanostructured lipid carriers: a comparative study.

    PubMed

    Babaei, S; Ghanbarzadeh, S; Adib, Z M; Kouhsoltani, M; Davaran, S; Hamishehkar, H

    2016-05-01

    Lipid based nanoparticles have become a major research object in topical drug delivery to enable drugs to pass the stratum corneum and reach the desired skin layer. The present investigation deals with the encapsulation of lidoacine into nanostructured lipid carriers (NLCs) and nanoethosomes for improving its dermal delivery and consequently local anesthetic efficacy. Concurrently these two topical delivery systems were compared. Lidocaine-loaded NLCs and nanoethosomes were characterized by various techniques and used for an in vitro skin penetration study using excised rat skin and Franz diffusion cells. The nanoparticles were tracked in the skin by following the Rhodamine-labled nanocarriers under fluorescent microscopy. Optimized lidocaine-loaded NLCs (size 96 nm, zeta potential -13.7 mV, encapsulation efficiency (EE) % 69.86% and loading capacity (LC) % 10.47%) and nanoethosomes (size 105.4 nm, zeta potential -33.6 mV, EE 40.14% and LC 8.02%) were chosen for a skin drug delivery study. Higher skin drug deposition of NLCs and nanoethosomal formulations compared to lidocaine hydroalcoholic solution represented a better localization of the drug in the skin. NLC formulation showed the lowest entered drug in the receptor phase of Franz diffusion cell in comparison with nanoethosomes and hydroalcoholic solution confirming the highest skin accumulation of drug. Both colloidal systems showed superiority over the drug solution for dermal delivery of lidocaine, however, NLC exhibited more promising characteristics than nanoethosomes regarding drug loading and skin targeted delivery.

  19. Formulation, Characterization and Pulmonary Deposition of Nebulized Celecoxib Encapsulated Nanostructured Lipid Carriers

    PubMed Central

    Patlolla, Ram R.; Chougule, Mahavir; Patel, Apurva R.; Jackson, Tanise; Tata, Prasad NV; Singh, Mandip

    2010-01-01

    The aim of the current study was to encapsulate celecoxib (Cxb) in the Nanostructured Lipid Carrier (Cxb-NLC) nanoparticles and evaluate the lung disposition of nanoparticles following nebulization in Balb/c mice. Cxb-NLC nanoparticles were prepared with Cxb, Compritol, Miglyol and sodium taurocholate using high-pressure homogenization. Cxb-NLC nanoparticles were characterized for physical and aerosol properties. In-vitro cytotoxicity studies were performed with A549 cells. The lung deposition and pharmacokinetic parameters of Cxb-NLC and Cxb solution (Cxb-Soln) formulations were determined using Inexpose™ system and Pari LC star jet nebulizer. The particle size and entrapment efficiency of Cxb-NLC formulation were 217 ± 20 nm and > 90%, respectively. The Cxb-NLC released the drug in controlled fashion, and in vitro aersolization of Cxb-NLC formulation showed FPF of 75.6 ± 4.6 %, MMAD of 1.6 ±0.13 μm and GSD of 1.2 ± 0.21. Cxb-NLC showed dose and time dependent cytotoxicity against A549 cells. Nebulization of Cxb-NLC demonstrated 4 fold higher AUCt/D in lung tissues compared to Cxb-Soln. The systemic clearance of Cxb-NLC was slower (0.93 L/h) compared to Cxb-Soln (20.03 L/h). Cxb encapsulated NLC were found to be stable and aerodynamic properties were within the respirable limits. Aerosolization of Cxb-NLC improved the Cxb pulmonary bioavailability compared to solution formulation which will potentially lead to better patient compliance with minimal dosing intervals. PMID:20153385

  20. High payload nanostructured lipid carriers fabricated with alendronate/polyethyleneimine ion complexes.

    PubMed

    Abd El-Hamid, Basma N; Swarnakar, Nitin K; Soliman, Ghareb M; Attia, Mohamed A; Pauletti, Giovanni M

    2018-01-15

    Oral bioavailability of the anti-osteoporotic drug alendronate (AL) is limited to ≤ 1% due to unfavorable physicochemical properties. To augment absorption across the gastrointestinal mucosa, an ion pair complex between AL and polyethyleneimine (PEI) was formed and incorporated into nanostructured lipid carriers (NLCs) using a modified solvent injection method. When compared to free AL, ion pairing with PEI increased drug encapsulation efficiency in NLCs from 10% to 87%. Drug release from NLCs measured in vitro using fasted state simulated intestinal fluid, pH 6.5 (FaSSIF-V2) was significantly delayed after PEI complexation. Stability of AL/PEI was pH-dependent resulting in 10-fold faster dissociation of AL in FaSSIF-V2 than measured at pH 7.4. Intestinal permeation properties estimated in vitro across Caco-2 cell monolayers revealed a 3-fold greater flux of AL encapsulated as hydrophobic ion complex in NLCs when compared to AL solution (P app  = 8.43 ± 0.14 × 10 -6 cm/s and vs. 2.76 ± 0.42 × 10 -6 cm/s). Cellular safety of AL/PEI-containing NLCs was demonstrated up to an equivalent AL concentration of 2.5 mM. These results suggest that encapsulation of AL/PEI in NLCs appears a viable drug delivery strategy for augmenting oral bioavailability of this clinically relevant bisphosphonate drug and, simultaneously, increase gastrointestinal safety. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Fabrication and magnetic properties of Ni nanospheres encapsulated in a fullerene-like carbon.

    PubMed

    Pol, S V; Pol, V G; Frydman, A; Churilov, G N; Gedanken, A

    2005-05-19

    A very simple, efficient, and economical synthetic technique, which produces fascinating fullerene-like Ni-C (graphitic) core-shell nanostructures at a relatively low temperature, is reported. The thermal dissociation of Ni acetylacetonate is carried out in a closed vessel cell (Swagelok) that was heated at 700 degrees C for 3 h. The encapsulation of ferromagnetic Ni nanospheres into the onion structured graphitic layers is obtained in a one-stage, single precursor reaction, without a catalyst, that possesses interesting magnetic properties. The magnetoresistance (MR) property of Ni nanospheres encapsulated in a fullerene-like carbon was measured, which shows large negative MR, of the order of 10%. The proposed mechanism for the formation of the Ni-C core-shell system is based on the segregation and the surface flux formed in the Ni and carbon particles during the reaction under autogenic pressure at elevated temperature.

  2. Iridium Clusters Encapsulated in Carbon Nanospheres as Nanocatalysts for Methylation of (Bio)Alcohols.

    PubMed

    Liu, Qiang; Xu, Guoqiang; Wang, Zhendong; Liu, Xiaoran; Wang, Xicheng; Dong, Linlin; Mu, Xindong; Liu, Huizhou

    2017-12-08

    C-H methylation is an attractive chemical transformation for C-C bonds construction in organic chemistry, yet efficient methylation of readily available (bio)alcohols in water using methanol as sustainable C1 feedstock is limited. Herein, iridium nanocatalysts encapsulated in yolk-shell-structured mesoporous carbon nanospheres (Ir@YSMCNs) were synthesized for this transformation. Monodispersed Ir clusters (ca. 1.0 nm) were encapsulated in situ and spatially isolated within YSMCNs by a silica-assisted sol-gel emulsion strategy. A selection of (bio)alcohols (19 examples) was selectively methylated in aqueous phase with good-to-high yields over the developed Ir@YSMCNs. The improved catalytic efficiencies in terms of activity and selectivity together with the good stability and recyclability were contributable to the ultrasmall Ir clusters with oxidation chemical state as a consequence of the confinement effect of YSMCNs with interconnected nanostructures. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Enhanced Mechanical Stability of Gold Nanotips through Carbon Nanocone Encapsulation

    PubMed Central

    Cano-Marquez, Abraham G.; Schmidt, Wesller G.; Ribeiro-Soares, Jenaina; Gustavo Cançado, Luiz; Rodrigues, Wagner N.; Santos, Adelina P.; Furtado, Clascidia A.; Autreto, Pedro A.S.; Paupitz, Ricardo; Galvão, Douglas S.; Jorio, Ado

    2015-01-01

    Gold is a noble metal that, in comparison with silver and copper, has the advantage of corrosion resistance. Despite its high conductivity, chemical stability and biocompatibility, gold exhibits high plasticity, which limits its applications in some nanodevices. Here, we report an experimental and theoretical study on how to attain enhanced mechanical stability of gold nanotips. The gold tips were fabricated by chemical etching and further encapsulated with carbon nanocones via nanomanipulation. Atomic force microscopy experiments were carried out to test their mechanical stability. Molecular dynamics simulations show that the encapsulated nanocone changes the strain release mechanisms at the nanoscale by blocking gold atomic sliding, redistributing the strain along the whole nanostructure. The carbon nanocones are conducting and can induce magnetism, thus opening new avenues on the exploitation of transport, mechanical and magnetic properties of gold covered by sp2 carbon at the nanoscale. PMID:26083864

  4. 21 CFR 520.1044c - Gentamicin sulfate soluble powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate soluble powder. 520.1044c... Gentamicin sulfate soluble powder. (a) Specifications. Each gram of gentamicin sulfate soluble powder contains gentamicin sulfate equivalent to 16.7, 66.7, or 333.3 milligrams of gentamicin. (b) Sponsor. See...

  5. 21 CFR 520.1044c - Gentamicin sulfate soluble powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate soluble powder. 520.1044c... Gentamicin sulfate soluble powder. (a) Specifications. Each gram of gentamicin sulfate soluble powder contains gentamicin sulfate equivalent to 16.7, 66.7, or 333.3 milligrams of gentamicin. (b) Sponsor. See...

  6. (Poly)cation-induced protection of conventional and wireframe DNA origami nanostructures.

    PubMed

    Ahmadi, Yasaman; De Llano, Elisa; Barišić, Ivan

    2018-04-26

    DNA nanostructures hold immense potential to be used for biological and medical applications. However, they are extremely vulnerable towards salt depletion and nucleases, which are common under physiological conditions. In this contribution, we used chitosan and linear polyethyleneimine for coating and long-term stabilization of several three-dimensional DNA origami nanostructures. The impact of the degree of polymerization and the charge density of the polymer together with the N/P charge ratio (ratio of the amines in polycations to the phosphates in DNA) on the stability of encapsulated DNA origami nanostructures in the presence of nucleases and in low-salt media was examined. The polycation shells were compatible with enzyme- and aptamer-based functionalization of the DNA nanostructures. Additionally, we showed that despite being highly vulnerable to salt depletion and nucleolytic digestion, self-assembled DNA nanostructures are stable in cell culture media up to a week. This was contrary to unassembled DNA scaffolds that degraded in one hour, showing that placing DNA strands into a spatially designed configuration crucially affect the structural integrity. The stability of naked DNA nanostructures in cell culture was shown to be mediated by growth media. DNA origami nanostructures kept in growth media were significantly more resistant towards low-salt denaturation, DNase I and serum-mediated digestion than when in a conventional buffer. Moreover, we confirmed that DNA origami nanostructures remain not only structurally intact but also fully functional after exposure to cell media. Agarose gel electrophoresis and negative stain transmission electron microscopy analysis revealed the hybridization of DNA origami nanostructures to their targets in the presence of serum proteins and nucleases. The structural integrity and functionality of DNA nanostructures in physiological fluids validate their use particularly for short-time biological applications in which the shape and structural details of DNA nanodevices are functionally critical.

  7. Loss of the homotypic fusion and vacuole protein sorting or golgi-associated retrograde protein vesicle tethering complexes results in gentamicin sensitivity in the yeast Saccharomyces cerevisiae.

    PubMed

    Wagner, Mark C; Molnar, Elizabeth E; Molitoris, Bruce A; Goebl, Mark G

    2006-02-01

    Gentamicin continues to be a primary antibiotic against gram-negative infections. Unfortunately, associated nephro- and ototoxicity limit its use. Our previous mammalian studies showed that gentamicin is trafficked to the endoplasmic reticulum in a retrograde manner and subsequently released into the cytosol. To better dissect the mechanism through which gentamicin induces toxicity, we have chosen to study its toxicity using the simple eukaryote Saccharomyces cerevisiae. A recent screen of the yeast deletion library identified multiple gentamicin-sensitive strains, many of which participate in intracellular trafficking. Our approach was to evaluate gentamicin sensitivity under logarithmic growth conditions. By quantifying growth inhibition in the presence of gentamicin, we determined that several of the sensitive strains were part of the Golgi-associated retrograde protein (GARP) and homotypic fusion and vacuole protein sorting (HOPS) complexes. Further evaluation of their other components showed that the deletion of any GARP member resulted in gentamicin-hypersensitive strains, while the deletion of other HOPS members resulted in less gentamicin sensitivity. Other genes whose deletion resulted in gentamicin hypersensitivity included ZUO1, SAC1, and NHX1. Finally, we utilized a Texas Red gentamicin conjugate to characterize gentamicin uptake and localization in both gentamicin-sensitive and -insensitive strains. These studies were consistent with our mammalian studies, suggesting that gentamicin toxicity in yeast results from alterations to intracellular trafficking pathways. The identification of genes whose absence results in gentamicin toxicity will help target specific pathways and mechanisms that contribute to gentamicin toxicity.

  8. Loss of the Homotypic Fusion and Vacuole Protein Sorting or Golgi-Associated Retrograde Protein Vesicle Tethering Complexes Results in Gentamicin Sensitivity in the Yeast Saccharomyces cerevisiae†

    PubMed Central

    Wagner, Mark C.; Molnar, Elizabeth E.; Molitoris, Bruce A.; Goebl, Mark G.

    2006-01-01

    Gentamicin continues to be a primary antibiotic against gram-negative infections. Unfortunately, associated nephro- and ototoxicity limit its use. Our previous mammalian studies showed that gentamicin is trafficked to the endoplasmic reticulum in a retrograde manner and subsequently released into the cytosol. To better dissect the mechanism through which gentamicin induces toxicity, we have chosen to study its toxicity using the simple eukaryote Saccharomyces cerevisiae. A recent screen of the yeast deletion library identified multiple gentamicin-sensitive strains, many of which participate in intracellular trafficking. Our approach was to evaluate gentamicin sensitivity under logarithmic growth conditions. By quantifying growth inhibition in the presence of gentamicin, we determined that several of the sensitive strains were part of the Golgi-associated retrograde protein (GARP) and homotypic fusion and vacuole protein sorting (HOPS) complexes. Further evaluation of their other components showed that the deletion of any GARP member resulted in gentamicin-hypersensitive strains, while the deletion of other HOPS members resulted in less gentamicin sensitivity. Other genes whose deletion resulted in gentamicin hypersensitivity included ZUO1, SAC1, and NHX1. Finally, we utilized a Texas Red gentamicin conjugate to characterize gentamicin uptake and localization in both gentamicin-sensitive and -insensitive strains. These studies were consistent with our mammalian studies, suggesting that gentamicin toxicity in yeast results from alterations to intracellular trafficking pathways. The identification of genes whose absence results in gentamicin toxicity will help target specific pathways and mechanisms that contribute to gentamicin toxicity. PMID:16436714

  9. Nanohelices from planar polymer self-assembled in carbon nanotubes

    PubMed Central

    Fu, Hongjin; Xu, Shuqiong; Li, Yunfang

    2016-01-01

    The polymer possessing with planar structure can be activated and guided to encapsulate the inner space of SWNT and form a helix through van der Waals interaction and the π-π stacking effect between the polymer and the inner surface of SWNT. The SWNT size, the nanostructure and flexibility of polymer chain are all determine the final structures. The basic interaction between the polymer and the nanotubes is investigated, and the condition and mechanism of the helix-forming are explained particularly. Hybrid polymers improve the ability of the helix formation. This study provides scientific basis for fabricating helical polymers encapsulated in SWNTs and eventually on their applications in various areas. PMID:27440493

  10. Micro/nanofabricated environments for synthetic biology.

    PubMed

    Collier, C Patrick; Simpson, Michael L

    2011-08-01

    A better understanding of how confinement, crowding and reduced dimensionality modulate reactivity and reaction dynamics will aid in the rational and systematic discovery of functionality in complex biological systems. Artificial microfabricated and nanofabricated structures have helped elucidate the effects of nanoscale spatial confinement and segregation on biological behavior, particularly when integrated with microfluidics, through precise control in both space and time of diffusible signals and binding interactions. Examples of nanostructured interfaces for synthetic biology include the development of cell-like compartments for encapsulating biochemical reactions, nanostructured environments for fundamental studies of diffusion, molecular transport and biochemical reaction kinetics, and regulation of biomolecular interactions as functions of microfabricated and nanofabricated topological constraints. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Albumin/gentamicin microspheres produced by supercritical assisted atomization: optimization of size, drug loading and release.

    PubMed

    Della Porta, G; Adami, R; Del Gaudio, P; Prota, L; Aquino, R; Reverchon, E

    2010-11-01

    In this work, the supercritical assisted atomization (SAA) is proposed, for the first time, not only as a micronization technology but also as a thermal coagulation process for the production of bovine serum albumin (BSA) microspheres charged with Gentamicin sulfate (GS). Particularly, different water solutions of BSA/GS were processed by SAA to produce protein microspheres with different size and antibiotic content. SAA precipitation temperature was selected in the range 100-130 °C to generate protein coagulation and to recover micronized BSA in form of hydrophobic aggregates; GS loading was varied between 10% and 50% (w/w) with an encapsulation efficiency which often reached 100%. In all cases, spherical and noncoalescing particles were successfully produced with a mean particle size of 2 µm and with a standard deviation of about ±1 µm. The microspheres also showed a good stability and constant water content after 60 days of storage. The release profiles of the entrapped drug were monitored using Franz cells to evaluate the possible application of the produced microspheres in wound dressing formulations. Particularly, the microspheres with a BSA/GS ratio of 4:1 after the first burst effect (of 40% of GS loaded) were able to release the GS continuously over 10 days. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  12. Nanostructures as promising tools for delivery of antimicrobial peptides.

    PubMed

    Brandelli, A

    2012-07-01

    Antimicrobial peptides have been extensively investigated for their potential applications as therapeutics and food biopreservatives. The antimicrobial activity may be impaired by the susceptibility for proteolytic degradation and undesirable interactions of the antimicrobial peptide in the biological environment. Development of nanostructures for entrapment and delivery of antimicrobial peptides may represent an alternative to the direct application of these substances. Lipid nanovesicles have been developed for encapsulation of antimicrobial peptides. Phosphatidylcholine is often employed in liposome manufacture, which is mostly achieved by the thin-film hydration method. Nanofibers may allow different physical modes of drug loading, including direct adsorption on the nanofiber surface or the assembly of drug-loaded nanoparticles. Self-assembled peptides reveal attractive features as nanostructures for applications in drug delivery and promising as antimicrobial agent for treatment of brain infections. Magnetic nanoparticles and nanotubules are also potential structures for entrapment of antimicrobial peptides. Nanoparticles can be also chemically modified with specific cell surface ligands to enhance cell adhesion and site specific delivery. This article reviews the most important nanostructures as promising tools for peptide delivery systems.

  13. Electronic Structure Control of Sub-nanometer 1D SnTe via Nanostructuring within Single-Walled Carbon Nanotubes.

    PubMed

    Vasylenko, Andrij; Marks, Samuel; Wynn, Jamie M; Medeiros, Paulo V C; Ramasse, Quentin M; Morris, Andrew J; Sloan, Jeremy; Quigley, David

    2018-05-25

    Nanostructuring, e. g., reduction of dimensionality in materials, offers a viable route toward regulation of materials electronic and hence functional properties. Here, we present the extreme case of nanostructuring, exploiting the capillarity of single-walled carbon nanotubes (SWCNTs) for the synthesis of the smallest possible SnTe nanowires with cross sections as thin as a single atom column. We demonstrate that by choosing the appropriate diameter of a template SWCNT, we can manipulate the structure of the quasi-one-dimensional (1D) SnTe to design electronic behavior. From first principles, we predict the structural re-formations that SnTe undergoes in varying encapsulations and confront the prediction with TEM imagery. To further illustrate the control of physical properties by nanostructuring, we study the evolution of transport properties in a homologous series of models of synthesized and isolated SnTe nanowires varying only in morphology and atomic layer thickness. This extreme scaling is predicted to significantly enhance thermoelectric performance of SnTe, offering a prospect for further experimental studies and future applications.

  14. Packaging DNA Origami into Viral Protein Cages.

    PubMed

    Linko, Veikko; Mikkilä, Joona; Kostiainen, Mauri A

    2018-01-01

    The DNA origami technique is a widely used method to create customized, complex, spatially well-defined two-dimensional (2D) and three-dimensional (3D) DNA nanostructures. These structures have huge potential to serve as smart drug-delivery vehicles and molecular devices in various nanomedical and biotechnological applications. However, so far only little is known about the behavior of these novel structures in living organisms or in cell culture/tissue models. Moreover, enhancing pharmacokinetic bioavailability and transfection properties of such structures still remains a challenge. One intriguing approach to overcome these issues is to coat DNA origami nanostructures with proteins or lipid membranes. Here, we show how cowpea chlorotic mottle virus (CCMV) capsid proteins (CPs) can be used for coating DNA origami nanostructures. We present a method for disassembling native CCMV particles and isolating the pure CP dimers, which can further bind and encapsulate a rectangular DNA origami shape. Owing to the highly programmable nature of DNA origami, packaging of DNA nanostructures into viral protein cages could find imminent uses in enhanced targeting and cellular delivery of various active nano-objects, such as enzymes and drug molecules.

  15. Effect of Protein Binding on the Activity of Penicillins in Combination with Gentamicin Against Enterococci

    PubMed Central

    Glew, Richard H.; Moellering, Robert C.

    1979-01-01

    To assess the effect of protein binding by human serum on the synergistic interaction of penicillins with gentamicin, time-kill curves were determined for four penicillins alone and in combination with gentamicin against 10 blood isolates of enterococci. Killing curves demonstrated synergism with penicillin G plus gentamicin against all 10 strains in either broth or 50% human serum. In broth the combinations of nafcillin plus gentamicin and oxacillin plus gentamicin were synergistic against 10 of 10 strains and 4 of 10 strains, respectively. However, in serum, nafcillin plus gentamicin was synergistically bactericidal against only two strains and oxacillin plus gentamicin against none. Methicillin plus gentamicin was synergistic against none of the enterococci in either medium. Thus, the semisynthetic, penicillinase-resistant penicillins are unlikely to be effective in the therapy of patients with enterococcal endocarditis. PMID:426508

  16. 21 CFR 524.1044c - Gentamicin sulfate ophthalmic ointment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate ophthalmic ointment. 524.1044c... § 524.1044c Gentamicin sulfate ophthalmic ointment. (a) Specifications. Each gram of ointment contains gentamicin sulfate equivalent to 3 milligrams of gentamicin. (b) Sponsors. See Nos. 000061 and 043264 in...

  17. 21 CFR 524.1044c - Gentamicin sulfate ophthalmic ointment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate ophthalmic ointment. 524.1044c... § 524.1044c Gentamicin sulfate ophthalmic ointment. (a) Specifications. Each gram of ointment contains gentamicin sulfate equivalent to 3 milligrams of gentamicin. (b) Sponsors. See Nos. 000061 and 025463 in...

  18. 21 CFR 524.1044c - Gentamicin sulfate ophthalmic ointment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate ophthalmic ointment. 524.1044c... § 524.1044c Gentamicin sulfate ophthalmic ointment. (a) Specifications. Each gram of ointment contains gentamicin sulfate equivalent to 3 milligrams of gentamicin. (b) Sponsors. See Nos. 000061 and 025463 in...

  19. 21 CFR 524.1044c - Gentamicin sulfate ophthalmic ointment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate ophthalmic ointment. 524.1044c... § 524.1044c Gentamicin sulfate ophthalmic ointment. (a) Specifications. Each gram of ointment contains gentamicin sulfate equivalent to 3 milligrams of gentamicin. (b) Sponsors. See Nos. 000061 and 025463 in...

  20. Nanostructured lipid dispersions for topical administration of crocin, a potent antioxidant from saffron (Crocus sativus L.).

    PubMed

    Esposito, Elisabetta; Drechsler, Markus; Mariani, Paolo; Panico, Anna Maria; Cardile, Venera; Crascì, Lucia; Carducci, Federica; Graziano, Adriana Carol Eleonora; Cortesi, Rita; Puglia, Carmelo

    2017-02-01

    Crocin, a potent antioxidant obtained from saffron, shows anticancer activity in in vivo models. Unfortunately unfavorable physicochemical features compromise its use in topical therapy. The present study describes the preparation and characterization of nanostructured lipid dispersions as drug delivery systems for topical administration of crocin and the evaluation of antioxidant and antiproliferative effects of crocin once encapsulated into nanostructured lipid dispersions. Nanostructured lipid dispersions based on monoolein in mixture with sodium cholate and sodium caseinate have been characterized by cryo-TEM and PCS. Crocin permeation was evaluated in vitro by Franz cells, while the oxygen radical absorbance capacity assay was used to evaluate the antioxidant activity. Furthermore, the antiproliferative activity was tested in vitro by the MTT test using a human melanoma cell line. The emulsification of monoolein with sodium cholate and sodium caseinate led to dispersions of cubosomes, hexasomes, sponge systems and vesicles, depending on the employed emulsifiers. Permeation and shelf life studies demonstrated that nanostructured lipid dispersions enabled to control both rate of crocin diffusion through the skin and crocin degradation. The oxygen radical absorbance capacity assay pointed out an interesting and prolonged antioxidant activity of crocin while the MTT test showed an increase of crocin cytotoxic effect after incorporation in nanostructured lipid dispersions. This work has highlighted that nanostructured lipid dispersions can protect the labile molecule crocin from degradation, control its skin diffusion and prolong antioxidant activity, therefore suggesting the suitability of nanostructured lipid dispersions for crocin topical administration. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Rapid colorimetric assay for gentamicin injection.

    PubMed

    Tarbutton, P

    1987-01-01

    A rapid colorimetric method for determining gentamicin concentration in commercial preparations of gentamicin sulfate injection was developed. Methods currently available for measuring gentamicin concentration via its colored complex with cupric ions in alkaline solution were modified to reduce the time required for a single analysis. The alkaline copper tartrate (ACT) reagent solution was prepared such that each milliliter contained 100 mumol cupric sulfate, 210 mumol potassium sodium tartrate, and 1.25 mmol sodium hydroxide. The assay involves mixing 0.3 mL gentamicin sulfate injection 40 mg/mL (of gentamicin), 1.0 mL ACT reagent, and 0.7 mL water; the absorbance of the resulting solution at 560 nm was used to calculate the gentamicin concentration in the sample. For injections containing 10 mg/mL of gentamicin, the amount of the injection was increased to 0.5 mL and water decreased to 0.5 mL. The concentration of gentamicin in samples representing 11 lots of gentamicin sulfate injection 40 mg/mL and 8 lots of gentamicin sulfate injection 10 mg/mL was determined. The specificity, reproducibility, and accuracy of the assay were assessed. The colored complex was stable for at least two hours. Gentamicin concentration ranged from 93.7 to 108% and from 95 to 109% of the stated label value of the 40 mg/mL and the 10 mg/mL injections, respectively. No components of the preservative system present in the injections interfered with the assay. Since other aminoglycosides produced a colored complex, the assay is not specific for gentamicin. The assay was accurate and reproducible over the range of 4-20 mg of gentamicin. This rapid and accurate assay can be easily applied in the hospital pharmacy setting.

  2. 21 CFR 520.1044a - Gentamicin sulfate oral solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate oral solution. 520.1044a... Gentamicin sulfate oral solution. (a) Specifications. Each milliliter of aqueous solution contains gentamicin sulfate equivalent to 50 milligrams of gentamicin. (b) Sponsor. See Nos. 000061 and 054925 in § 510.600(c...

  3. 21 CFR 520.1044a - Gentamicin sulfate oral solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate oral solution. 520.1044a... Gentamicin sulfate oral solution. (a) Specifications. Each milliliter of aqueous solution contains gentamicin sulfate equivalent to 50 milligrams of gentamicin. (b) Sponsor. See Nos. 000061 and 054925 in § 510.600(c...

  4. 21 CFR 520.1044a - Gentamicin sulfate oral solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate oral solution. 520.1044a... Gentamicin sulfate oral solution. (a) Specifications. Each milliliter of aqueous solution contains gentamicin sulfate equivalent to 50 milligrams of gentamicin. (b) Sponsor. See Nos. 000061 and 054925 in § 510.600(c...

  5. 21 CFR 520.1044c - Gentamicin sulfate powder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate powder. 520.1044c Section 520... sulfate powder. (a) Specifications. Each gram of powder contains gentamicin sulfate equivalent to: (1) 16... colibacillosis: Gentamicin sulfate equivalent to 25 mg of gentamicin per gallon of drinking water to provide 0.5...

  6. 21 CFR 520.1044c - Gentamicin sulfate powder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate powder. 520.1044c Section 520... sulfate powder. (a) Specifications. Each gram of powder contains gentamicin sulfate equivalent to: (1) 16... colibacillosis: Gentamicin sulfate equivalent to 25 mg of gentamicin per gallon of drinking water to provide 0.5...

  7. 21 CFR 520.1044a - Gentamicin sulfate oral solution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate oral solution. 520.1044a... Gentamicin sulfate oral solution. (a) Specifications. Each milliliter of aqueous solution contains gentamicin sulfate equivalent to 50 milligrams of gentamicin. (b) Sponsor. See Nos. 000061 and 054925 in § 510.600(c...

  8. Super-hydrophobic yolk-shell nanostructure with enhanced catalytic performance in the reduction of hydrophobic nitroaromatic compounds.

    PubMed

    Shi, Song; Wang, Min; Chen, Chen; Gao, Jin; Ma, Hong; Ma, Jiping; Xu, Jie

    2013-10-25

    A self-templating method to fabricate a super-hydrophobic yolk-shell nano-reactor was reported. Metal nanoparticles were encapsulated in the porous super-hydrophobic shell. This super-hydrophobic catalyst showed excellent performance in the reduction of nitroaromatic compounds in aqueous phase and a positive correlation was found between the reaction rate and the hydrophobicity of the substrate.

  9. Anisotropic nanomaterials: Synthesis, optical and magnetic properties, and applications

    NASA Astrophysics Data System (ADS)

    Banholzer, Matthew John

    As nanoscience and nanotechnology mature, anisotropic metal nanostructures are emerging in a variety of contexts as valuable class of nanostructures due to their distinctive attributes. With unique properties ranging from optical to magnetic and beyond, these structures are useful in many new applications. Chapter two discusses the nanodisk code: a linear array of metal disk pairs that serve as surface-enhanced Raman scattering substrates. These multiplexing structures employ a binary encoding scheme, perform better than previous nanowires designs (in the context of SERS) and are useful for both convert encoding and tagging of substrates (based both on spatial disk position and spectroscopic response) as well as biomolecule detection (e.g. DNA). Chapter three describes the development of improved, silver-based nanodisk code structures. Work was undertaken to generate structures with high yield and reproducibility and to reoptimize the geometry of each disk pair for maximum Raman enhancement. The improved silver structures exhibit greater enhancement than Au structures (leading to lower DNA detection limits), convey additional flexibility, and enable trinary encoding schemes where far more unique structures can be created. Chapter four considers the effect of roughness on the plasmonic properties of nanorod structures and introduces a novel method to smooth the end-surfaces of nanorods structures. The smoothing technique is based upon a two-step process relying upon diffusion control during nanowires growth and selective oxidation after each step of synthesis is complete. Empirical and theoretical work show that smoothed nanostructures have superior and controllable optical properties. Chapter five concerns silica-encapsulated gold nanoprisms. This encapsulation allows these highly sensitive prisms to remain stable and protected in solution, enabling their use as class-leading sensors. Theoretical study complements the empirical work, exploring the effect of encapsulation on the SPR of these structures. Chapter six focuses on the magnetic properties of Au-Ni heterostructures. In addition to demonstration of nanoconfinement effects based upon the anisotropy of the nanorods/nanodisk structure, the magnetic coupling of rod-disk heterostructures is examined. Subsequent investigations suggest that the magnetic behavior of disks can be influenced by nearby rod segments, leading to the creation of a three-state spin system that may prove useful in device applications.

  10. Spirulina platensis protects against renal injury in rats with gentamicin-induced acute tubular necrosis.

    PubMed

    Avdagić, Nesina; Cosović, Esad; Nakas-Ićindić, Emina; Mornjaković, Zakira; Zaciragić, Asija; Hadzović-Dzuvo, Almira

    2008-11-01

    The present study was carried out to evaluate the renoprotective antioxidant effect of Spirulina platensis on gentamicin-induced acute tubular necrosis in rats. Albino-Wistar rats, (9male and 9 female), weighing approximately 250 g, were used for this study. Rats were randomly assigned to three equal groups. Control group received 0,9 % sodium chloride intraperitoneally for 7 days at the same volume as gentamicin group. Gentamicin group was treated intraperitoneally with gentamicin, 80 mg/kg daily for 7 days. Gentamicin+spirulina group received Spirulina platensis 1000 mg/kg orally 2 days before and 7 days concurrently with gentamicin (80 mg/kg i.p.). Nephrotoxicity was assessed by measuring plasma nitrite concentration, stabile metabolic product of nitric oxide with oxygen. Plasma nitrite concentration was determined by colorimetric method using Griess reaction. For histological analysis kidney specimens were stained with hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stain. Plasma nitrite concentration and the level of kidney damage were significantly higher in gentamicin group in comparison both to the control and gentamicin+spirulina group. Spirulina platensis significantly lowered the plasma nitrite level and attenuated histomorphological changes related to renal injury caused by gentamicin. Thus, the results from present study suggest that Spirulina platensis has renoprotective potential in gentamicin-induced acute tubular necrosis possibly due to its antioxidant properties.

  11. Synthesis of core-shell iron nanoparticles via a new (novel) approach

    NASA Astrophysics Data System (ADS)

    Chaudhary, Rakesh P.; Koymen, Ali R.

    2014-03-01

    Carbon-encapsulated iron (Fe) nanoparticles were synthesized by a newly developed method in toluene. Transmission Electron Microscopy (TEM) and High Resolution Transmission Electron Microscopy (HRTEM) of the as prepared sample reveal that core-shell nanostructures have been formed with Fe as core and graphitic carbon as shell. Fe nanoparticles with diameter 11nm to 102 nm are encapsulated by 6-8 nm thick graphitic carbon layers. There was no iron carbide formation observed between the Fe core and the graphitic shell. The Fe nanoparticles have body centered cubic (bcc) crystal structure. The magnetic hysteresis loop of the as synthesized powder at room temperature showed a saturation magnetization of 9 Am2 kg-1. After thermal treatment crystalline order of the samples improved and hence saturation magnetization increased to 24 Am2kg-1. We foresee that the carbon-encapsulated Fe nanoparticles are biologically friendly and could have potential applications in Magnetic Resonance Imaging (MRI) and Photothermal cancer therapy.

  12. Host-guest encapsulation of materials by assembled virus protein cages

    NASA Astrophysics Data System (ADS)

    Douglas, Trevor; Young, Mark

    1998-05-01

    Self-assembled cage structures of nanometre dimensions can be used as constrained environments for the preparation of nanostructured materials, and the encapsulation of guest molecules, with potential applications in drug delivery and catalysis. In synthetic systems the number of subunits contributing to cage structures is typically rather small,. But the protein coats of viruses (virions) commonly comprise hundreds of subunits that self-assemble into a cage for transporting viral nucleic acids. Many virions, moreover, can undergo reversible structural changes that open or close gated pores to allow switchable access to their interior. Here we show that such a virion - that of the cowpea chlorotic mottle virus - can be used as a host for the synthesis of materials. We report the mineralization of two polyoxometalate species (paratungstate and decavanadate) and the encapsulation of an anionic polymer inside this virion, controlled by pH-dependent gating of the virion's pores. The diversity in size and shape of such virus particles make this a versatile strategy for materials synthesis and molecular entrapment.

  13. Design of Magnetic Gelatine/Silica Nanocomposites by Nanoemulsification: Encapsulation versus in Situ Growth of Iron Oxide Colloids

    PubMed Central

    Allouche, Joachim; Chanéac, Corinne; Brayner, Roberta; Boissière, Michel; Coradin, Thibaud

    2014-01-01

    The design of magnetic nanoparticles by incorporation of iron oxide colloids within gelatine/silica hybrid nanoparticles has been performed for the first time through a nanoemulsion route using the encapsulation of pre-formed magnetite nanocrystals and the in situ precipitation of ferrous/ferric ions. The first method leads to bi-continuous hybrid nanocomposites containing a limited amount of well-dispersed magnetite colloids. In contrast, the second approach allows the formation of gelatine-silica core-shell nanostructures incorporating larger amounts of agglomerated iron oxide colloids. Both magnetic nanocomposites exhibit similar superparamagnetic behaviors. Whereas nanocomposites obtained via an in situ approach show a strong tendency to aggregate in solution, the encapsulation route allows further surface modification of the magnetic nanocomposites, leading to quaternary gold/iron oxide/silica/gelatine nanoparticles. Hence, such a first-time rational combination of nano-emulsion, nanocrystallization and sol-gel chemistry allows the elaboration of multi-component functional nanomaterials. This constitutes a step forward in the design of more complex bio-nanoplatforms. PMID:28344239

  14. Design of Magnetic Gelatine/Silica Nanocomposites by Nanoemulsification: Encapsulation versus in Situ Growth of Iron Oxide Colloids.

    PubMed

    Allouche, Joachim; Chanéac, Corinne; Brayner, Roberta; Boissière, Michel; Coradin, Thibaud

    2014-07-31

    The design of magnetic nanoparticles by incorporation of iron oxide colloids within gelatine/silica hybrid nanoparticles has been performed for the first time through a nanoemulsion route using the encapsulation of pre-formed magnetite nanocrystals and the in situ precipitation of ferrous/ferric ions. The first method leads to bi-continuous hybrid nanocomposites containing a limited amount of well-dispersed magnetite colloids. In contrast, the second approach allows the formation of gelatine-silica core-shell nanostructures incorporating larger amounts of agglomerated iron oxide colloids. Both magnetic nanocomposites exhibit similar superparamagnetic behaviors. Whereas nanocomposites obtained via an in situ approach show a strong tendency to aggregate in solution, the encapsulation route allows further surface modification of the magnetic nanocomposites, leading to quaternary gold/iron oxide/silica/gelatine nanoparticles. Hence, such a first-time rational combination of nano-emulsion, nanocrystallization and sol-gel chemistry allows the elaboration of multi-component functional nanomaterials. This constitutes a step forward in the design of more complex bio-nanoplatforms.

  15. Non-encapsulation approach for high-performance Li-S batteries through controlled nucleation and growth

    NASA Astrophysics Data System (ADS)

    Pan, Huilin; Chen, Junzheng; Cao, Ruiguo; Murugesan, Vijay; Rajput, Nav Nidhi; Han, Kee Sung; Persson, Kristin; Estevez, Luis; Engelhard, Mark H.; Zhang, Ji-Guang; Mueller, Karl T.; Cui, Yi; Shao, Yuyan; Liu, Jun

    2017-10-01

    High-surface-area, nanostructured carbon is widely used for encapsulating sulfur and improving the cyclic stability of Li-S batteries, but the high carbon content and low packing density limit the specific energy that can be achieved. Here we report an approach that does not rely on sulfur encapsulation. We used a low-surface-area, open carbon fibre architecture to control the nucleation and growth of the sulfur species by manipulating the carbon surface chemistry and the solvent properties, such as donor number and Li+ diffusivity. Our approach facilitates the formation of large open spheres and prevents the production of an undesired insulating sulfur-containing film on the carbon surface. This mechanism leads to 100% sulfur utilization, almost no capacity fading, over 99% coulombic efficiency and high energy density (1,835 Wh kg-1 and 2,317 Wh l-1). This finding offers an alternative approach for designing high-energy and low-cost Li-S batteries through controlling sulfur reaction on low-surface-area carbon.

  16. Targeted Cellular Drug Delivery using Tailored Dendritic Nanostructures

    NASA Astrophysics Data System (ADS)

    Kannan, Rangaramanujam; Kolhe, Parag; Kannan, Sujatha; Lieh-Lai, Mary

    2002-03-01

    Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorble, ‘peripheral’ functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug and gene delivery. The large number of end groups can also be tailored to create special affinity to targeted cells, and can also encapsulate drugs and deliver them in a controlled manner. We are developing tailor-modified dendritic systems for drug delivery. Synthesis, in-vitro drug loading, in-vitro drug delivery, and the targeting efficiency to the cell are being studied systematically using a wide variety of experimental tools. Polyamidoamine and Polyol dendrimers, with different generations and end-groups are studied, with drugs such as Ibuprofen and Methotrexate. Our results indicate that a large number of drug molecules can be encapsulated/attached to the dendrimers, depending on the end groups. The drug-encapsulated dendrimer is able to enter the cells rapidly and deliver the drug. Targeting strategies being explored

  17. Tunable Encapsulation Structure of Block Copolymer Coated Single-Walled Carbon Nanotubes in Aqueous Solution

    DOE PAGES

    Han, Youngkyu; Ahn, Suk-Kyun; Zhang, Zhe; ...

    2015-05-15

    The nano-sized and shape-tunable molecular building blocks can provide great opportunities for the fabrication of precisely controlled nanostructures. In this work, we have fabricated a molecular building block of single-walled carbon nanotubes (SWNTs) coated by PPO-PEO-PPO block copolymers whose encapsulation structure can be controlled via temperature or addition of small molecules. The structure and optical properties of SWNT-block copolymers have been investigated by small angle neutron scattering (SANS), ultraviolet-visible (UV-vis) spectroscopy, atomic force microscopy (AFM), and molecular dynamics (MD) simulation. The structure of the hydrated block copolymer layer surrounding SWNT can be controlled reversibly by varying temperature as well asmore » by irreversibly adding 5-methylsalicylic acid (5MS). Increasing hydrophobicity of the polymers with temperature and strong tendency of 5MS to interact with both block copolymers and orbitals of the SWNTs are likely to be responsible for the significant structural change of the block copolymer encapsulation layer, from loose corona shell to tightly encapsulating compact shell. These result shows an efficient and simple way to fabricate and manipulate carbon-based nano building blocks in aqueous systems with tunable structure.« less

  18. 77 FR 3598 - Ophthalmic and Topical Dosage Form New Animal Drugs; Gentamicin and Betamethasone Spray

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... veterinary prescription use of gentamicin sulfate and betamethasone valerate topical spray in dogs. DATES... prescription use of Gentamicin Topical Spray (gentamicin sulfate and betamethasone valerate) in dogs. Sparhawk...

  19. Photophysical studies on curcumin-sophorolipid nanostructures: applications in quorum quenching and imaging

    PubMed Central

    2018-01-01

    Sophorolipid biosurfactants are biodegradable, less toxic and FDA approved. The purified acidic form of sophorolipid is stimuli-responsive with self-assembling properties and used for solubilizing hydrophobic drugs. This study encapsulated curcumin (CU) with acidic sophorolipid (ASL) micelles and analysed using photophysical studies like UV-visible spectroscopy, photoluminescence (PL) spectroscopy and time-correlated single photon counting (TCSPC). TEM images have revealed ellipsoid micelles of approximately 100 nm size and were confirmed by dynamic light scattering. The bacterial fluorescence uptake studies showed the uptake of formed CUASL nanostructures into both Gram-positive and Gram-negative bacteria. They also showed quorum quenching activity against Pseudomonas aeruginosa. The results have demonstrated this system has potential theranostic applications. PMID:29515826

  20. The Role of Monitoring Gentamicin Levels in Patients with Gram-Negative Peritoneal Dialysis-Associated Peritonitis

    PubMed Central

    Tang, Wen; Cho, Yeoungjee; Hawley, Carmel M.; Badve, Sunil V.; Johnson, David W.

    2014-01-01

    ♦ Background: There is limited available evidence regarding the role of monitoring serum gentamicin concentrations in peritoneal dialysis (PD) patients receiving this antimicrobial agent in gram-negative PD-associated peritonitis. ♦ Methods: Using data collected in all patients receiving PD at a single center who experienced a gram-negative peritonitis episode between 1 January 2005 and 31 December 2011, we investigated the relationship between measured serum gentamicin levels on day 2 following initial empiric antibiotic therapy and subsequent clinical outcomes of confirmed gram-negative peritonitis. ♦ Results: Serum gentamicin levels were performed on day 2 in 51 (77%) of 66 first gram-negative peritonitis episodes. Average serum gentamicin levels on day 2 were 1.83 ± 0.84 mg/L with levels exceeding 2 mg/L in 22 (43%) cases. The overall cure rate was 64%. No cases of ototoxicity were observed. Day-2 gentamicin levels were not significantly different between patients who did and did not have a complication or cure. Using multivariable logistic regression analysis, failure to cure peritonitis was not associated with either day-2 gentamicin level (adjusted odds ratio (OR) 0.96, 95% confidence interval (CI) 0.25 - 3.73) or continuation of gentamicin therapy beyond day 2 (OR 0.28, 0.02 - 3.56). The only exception was polymicrobial peritonitis, where day-2 gentamicin levels were significantly higher in episodes that were cured (2.06 ± 0.41 vs 1.29 ± 0.71, p = 0.01). In 17 (26%) patients receiving extended gentamicin therapy, day-5 gentamicin levels were not significantly related to peritonitis cure. ♦ Conclusion: Day-2 gentamicin levels did not predict gentamicin-related harm or efficacy during short-course gentamicin therapy for gram-negative PD-related peritonitis, except in cases of polymicrobial peritonitis, where higher levels were associated with cure. PMID:24385334

  1. Gentamicin release from commercially-available gentamicin-loaded PMMA bone cements in a prosthesis-related interfacial gap model and their antibacterial efficacy.

    PubMed

    Neut, Daniëlle; Kluin, Otto S; Thompson, Jonathan; van der Mei, Henny C; Busscher, Henk J

    2010-11-10

    Around about 1970, a gentamicin-loaded poly (methylmethacrylate) (PMMA) bone cement brand (Refobacin Palacos R) was introduced to control infection in joint arthroplasties. In 2005, this brand was replaced by two gentamicin-loaded follow-up brands, Refobacin Bone Cement R and Palacos R + G. In addition, another gentamicin-loaded cement brand, SmartSet GHV, was introduced in Europe in 2003. In the present study, we investigated differences in gentamicin release and the antibacterial efficacy of the eluent between these four cement brands. 200 μm-wide gaps were made in samples of each cement and filled with buffer in order to measure the gentamicin release. Release kinetics were related to bone cement powder particle characteristics and wettabilities of the cement surfaces. Gaps were also inoculated with bacteria isolated from infected prostheses for 24 h and their survival determined. Gentamicin release and bacterial survival were statistically analysed using the Student's t-test. All three Palacos variants showed equal burst releases but each of the successor Palacos cements showed significantly higher sustained releases. SmartSet GHV showed a significantly higher burst release, while its sustained release was comparable with original Palacos. A gentamicin-sensitive bacterium did not survive in the high gentamicin concentrations in the interfacial gaps, while a gentamicin-resistant strain did, regardless of the type of cement used. Survival was independent of the level of burst release by the bone cement. Although marketed as the original gentamicin-loaded Palacos cement, orthopaedic surgeons should be aware that the successor cements do not appear to have the same release characteristics as the original one. Overall, high gentamicin concentrations were reached inside our prosthesis-related interfacial gap model. These concentrations may be expected to effectively decontaminate the prosthesis-related interfacial gap directly after implantation, provided that these bacteria are sensitive for gentamicin.

  2. SPIRULINA PLATENSIS PROTECTS AGAINST RENAL INJURY IN RATS WITH GENTAMICIN-INDUCED ACUTE TUBULAR NECROSIS

    PubMed Central

    Avdagić, Nesina; Ćosović, Esad; Nakaš-Ićindić, Emina; Mornjaković, Zakira; Začiragić, Asija; Hadžović-Džuvo, Almira

    2008-01-01

    The present study was carried out to evaluate the renoprotective antioxidant effect of Spirulina platensis on gentamicin-induced acute tubular necrosis in rats. Albino-Wistar rats, (9male and 9 female), weighing approximately 250 g, were used for this study. Rats were randomly assigned to three equal groups. Control group received 0,9 % sodium chloride intraperitoneally for 7 days at the same volume as gentamicin group. Gentamicin group was treated intraperitoneally with gentamicin, 80mg/kg daily for 7 days. Gentamicin+spirulina group received Spirulina platensis 1000 mg/kg orally 2 days before and 7 days concurrently with gentamicin (80mg/kg i.p.). Nephrotoxicity was assessed by measuring plasma nitrite concentration, stabile metabolic product of nitric oxide with oxygen. Plasma nitrite concentration was determined by colorimetric method using Griess reaction. For histological analysis kidney specimens were stained with hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stain. Plasma nitrite concentration and the level of kidney damage were significantly higher in gentamicin group in comparison both to the control and gentamicin+spirulina group. Spirulina platensis significantly lowered the plasma nitrite level and attenuated histomorphological changes related to renal injury caused by gentamicin. Thus, the results from present study suggest that Spirulina platensis has renoprotective potential in gentamicin-induced acute tubular necrosis possibly due to its antioxidant properties. PMID:19125703

  3. Enhancement of physico-chemical properties of the hydrophobic anticancer molecule following nanoencapsulation

    NASA Astrophysics Data System (ADS)

    Kumari, Anshu; Kumar, Amit; Gupta, Sharad

    2018-02-01

    Flavonoids are one of the important naturally available small molecules found in our daily diets. They have been considered as potential therapeutic agents for anticancer therapy. Despite their anti-cancer properties, their therapeutic application is very limited due to poor water solubility, which results in poor bioavailability to the diseased cells. Hence, to overcome this limitation of Flavonoids, Quercetin (Qct), the most extensively studied flavonoid, prompted us to encapsulate it within nanoparticles. We have successfully encapsulated Qct within cationic polymer based nanoparticles using simple two-step self-assembly fabrication method and studied its effect on absorption and emission properties of Qct. This study was aimed at Qct encapsulation and its effect on the optical properties of Qct for the diagnostic applications. Our results indicate that Qct was efficiently encapsulated within the polymeric nanoparticles. This resulted into 17 times increase in fluorescence emission of encapsulated Qct (Qct-NPs) in comparison with its aqueous suspension. Thus, Qct-NPs can be utilized as a fluorescent probe for various biomedical applications. These probes will have multiple functions integrated into a single nanostructure, enabling the Qct nanoparticles for imaging and therapy. This is the first report on the effect of nanoencapsulation on optical properties of Qct. Thus, Qct-NPs can be harnessed as an effective theranostic agent, and that will not only allow to image and but also treat the cancer in a single clinical procedure.

  4. Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis

    NASA Astrophysics Data System (ADS)

    Huang, Jia-Lin; Jiang, Gan; Song, Qing-Xiang; Gu, Xiao; Hu, Meng; Wang, Xiao-Lin; Song, Hua-Hua; Chen, Le-Pei; Lin, Ying-Ying; Jiang, Di; Chen, Jun; Feng, Jun-Feng; Qiu, Yong-Ming; Jiang, Ji-Yao; Jiang, Xin-Guo; Chen, Hong-Zhuan; Gao, Xiao-Ling

    2017-05-01

    Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to `drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras-activated cancers.

  5. Optimised NLC: a nanotechnological approach to improve the anaesthetic effect of bupivacaine.

    PubMed

    Rodrigues da Silva, Gustavo H; Ribeiro, Lígia N M; Mitsutake, Hery; Guilherme, Viviane A; Castro, Simone R; Poppi, Ronei J; Breitkreitz, Márcia C; de Paula, Eneida

    2017-08-30

    The short time of action and systemic toxicity of local anaesthetics limit their clinical application. Bupivacaine is the most frequently used local anaesthetic in surgical procedures worldwide. The discovery that its S(-) enantiomeric form is less toxic than the R(+) form led to the introduction of products with enantiomeric excess (S75:R25 bupivacaine) in the market. Nevertheless, the time of action of bupivacaine is still short; to overcome that, bupivacaine S75:R25 (BVC S75 ) was encapsulated in nanostructured lipid carriers (NLC). In this work, we present the development of the formulation using chemometric tools of experimental design to study the formulation factors and Raman mapping associated with Classical Least Squares (CLS) to study the miscibility of the solid and the liquid lipids. The selected formulation of the nanostructured lipid carrier containing bupivacaine S75:R25 (NLC BVC ) was observed to be stable for 12 months under room conditions regarding particle size, polydispersion, Zeta potential and encapsulation efficiency. The characterisation by DSC, XDR and TEM confirmed the encapsulation of BVC S75 in the lipid matrix, with no changes in the structure of the nanoparticles. The in vivo analgesic effect elicited by NLC BVC was twice that of free BVC S75 . Besides improving the time of action , no statistical difference in the blockage of the sciatic nerve of rats was found between 0.125% NLC BVC and 0.5% free BVC S75 . Therefore, the formulation allows a reduction in the required anaesthesia dose, decreasing the systemic toxicity of bupivacaine, and opening up new possibilities for different clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Nucleic acid-based nanoengineering: novel structures for biomedical applications

    PubMed Central

    Li, Hanying; LaBean, Thomas H.; Leong, Kam W.

    2011-01-01

    Nanoengineering exploits the interactions of materials at the nanometre scale to create functional nanostructures. It relies on the precise organization of nanomaterials to achieve unique functionality. There are no interactions more elegant than those governing nucleic acids via Watson–Crick base-pairing rules. The infinite combinations of DNA/RNA base pairs and their remarkable molecular recognition capability can give rise to interesting nanostructures that are only limited by our imagination. Over the past years, creative assembly of nucleic acids has fashioned a plethora of two-dimensional and three-dimensional nanostructures with precisely controlled size, shape and spatial functionalization. These nanostructures have been precisely patterned with molecules, proteins and gold nanoparticles for the observation of chemical reactions at the single molecule level, activation of enzymatic cascade and novel modality of photonic detection, respectively. Recently, they have also been engineered to encapsulate and release bioactive agents in a stimulus-responsive manner for therapeutic applications. The future of nucleic acid-based nanoengineering is bright and exciting. In this review, we will discuss the strategies to control the assembly of nucleic acids and highlight the recent efforts to build functional nucleic acid nanodevices for nanomedicine. PMID:23050076

  7. Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats.

    PubMed

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Suddek, Ghada M; Salem, Hatem A

    2015-12-01

    Gentamicin is a widely used antibiotic against serious and life-threatening infections; however, its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine whether flavocoxid has a protective effect against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of flavocoxid on gentamicin induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was determined. Twenty-four male Wistar albino rats were randomly divided into three groups, namely control, gentamicin (100 mg/kg, i.p.) and gentamicin plus flavocoxid (20 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood, urine samples and kidneys were collected for further analysis. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated renal somatic index (RSI), serum creatinine, blood urea nitrogen, serum lactate dehydrogenase, and protein in urine with a concomitant reduction in serum albumin and normalized creatinine clearance value as compared with the controls. Moreover, a significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione and superoxide dismutase activities was detected upon gentamicin administration together with increasing the sensitivity of isolated urinary bladder rings to ACh. Exposure to gentamicin induced necrosis of renal tubular epithelial cells. Flavocoxid protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by gentamicin treatment. In addition, flavocoxid significantly reduced the responses of isolated bladder rings to ACh. The results from our study indicate that flavocoxid supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells.

  8. Gentamicin ototoxicity: a 23-year selected case series of 103 patients.

    PubMed

    Ahmed, Rebekah M; Hannigan, Imelda P; MacDougall, Hamish G; Chan, Raymond C; Halmagyi, G Michael

    2012-06-18

    To review patients with severe bilateral vestibular loss associated with gentamicin treatment in hospital. A retrospective case series of presentations to a balance disorders clinic between 1988 and 2010. Relationship between vestibulotoxicity and gentamicin dose or dosing profile; indications for prescribing gentamicin. 103 patients (age, 18-84 years; mean, 64 years) presented with imbalance, oscillopsia or both, but none had vertigo. Only three noted some hearing impairment after having gentamicin, but audiometric thresholds for all patients were consistent with their age. In all patients, the following tests gave positive results: a bilateral clinical head-impulse test, a vertical head-shaking test for vertical oscillopsia, and a foam Romberg test. In 21 patients, imbalance occurred during gentamicin treatment (ignored or dismissed by prescribers in 20) and in 66 after treatment; the remaining 16 could not recall when symptoms were first noticed, except that it was after gentamicin treatment in hospital. Total gentamicin dose range was 2-318 mg/kg (mean, 52 mg/kg), daily dose range was 1.5-5.6 mg/kg (mean, 3.5mg/kg), and duration was 1-80 days (mean, 17 days). Six patients had only a single dose; 26 had five or fewer doses. Serum gentamicin levels, measured in 82 patients, were in the recommended range in 59. Time to diagnosis ranged from 4 days to 15 years. Nephrotoxicity developed in 43 patients. Gentamicin dosage complied with contemporary or current Australian antibiotic guidelines in under half the patients. Gentamicin ototoxicity is vestibular, not cochlear, producing permanent loss of balance, but not of hearing. Gentamicin can be vestibulotoxic in any dose, in any regimen, at any serum level.

  9. Nanostructured gellan and xanthan hydrogel depot integrated within a baghdadite scaffold augments bone regeneration.

    PubMed

    Sehgal, Rekha R; Roohani-Esfahani, S I; Zreiqat, Hala; Banerjee, Rinti

    2017-04-01

    Controlled delivery of biological cues through synthetic scaffolds to enhance the healing capacity of bone defects is yet to be realized clinically. The purpose of this study was development of a bioactive tissue-engineered scaffold providing the sustained delivery of an osteoinductive drug, dexamethasone disodium phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous baghdadite (BD; Ca 3 ZrSi 2 O 9 ) scaffolds, a zirconia-modified calcium silicate ceramic, was coated with DXP-encapsulated CN nanoparticles (DXP-CN) using nanostructured gellan and xanthan hydrogel (GX). Crosslinker and GX polymer concentrations were optimized to achieve a homogeneous distribution of hydrogel coating within BD scaffolds. Dynamic laser scattering indicated an average size of 521 ± 21 nm for the DXP-CN nanoparticles. In vitro drug-release studies demonstrated that the developed DXP-CN-GX hydrogel-coated BD scaffolds (DXP-CN-GX-BD) resulted in a sustained delivery of DXP over the 5 days (78 ± 6% of drug release) compared with burst release over 1 h, seen from free DXP loaded in uncoated BD scaffolds (92 ± 8% release in 1 h). To estimate the influence of controlled delivery of DXP from the developed scaffolds, the effect on MG 63 cells was evaluated using various bone differentiation assays. Cell culture within DXP-CN-GX-BD scaffolds demonstrated a significant increase in the expression of early and late osteogenic markers of alkaline phosphatase activity, collagen type 1 and osteocalcin, compared to the uncoated BD scaffold. The results suggest that the DXP-releasing nanostructured hydrogel integrated within the BD scaffold caused sustained release of DXP, improving the potential for osteogenic differentiation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig.

    PubMed

    Salt, A N; Hartsock, J J; Gill, R M; King, E; Kraus, F B; Plontke, S K

    2016-12-01

    Intratympanic gentamicin therapy is widely used clinically to suppress the vestibular symptoms of Meniere's disease. Dosing in humans was empirically established and we still know remarkably little about where gentamicin enters the inner ear, where it reaches in the inner ear and what time course it follows after local applications. In this study, gentamicin was applied to the round window niche as a 20 μL bolus of 40 mg/ml solution. Ten 2 μL samples of perilymph were collected sequentially from the lateral semi-circular canal (LSCC) at times from 1 to 4 h after application. Gentamicin concentration was typically highest in samples originating from the vestibule and was lower in samples originating from scala tympani. To interpret these results, perilymph elimination kinetics for gentamicin was quantified by loading the entire perilymph space by injection at the LSCC with a 500 μg/ml gentamicin solution followed by sequential perilymph sampling from the LSCC after different delay times. This allowed concentration decline in perilymph to be followed with time. Gentamicin was retained well in scala vestibuli and the vestibule but declined rapidly at the base of scala tympani, dominated by interactions of perilymph with CSF, as reported for other substances. Quantitative analysis, taking into account perilymph kinetics for gentamicin, showed that more gentamicin entered at the round window membrane (57%) than at the stapes (35%) but the lower concentrations found in scala tympani were due to greater losses there. The gentamicin levels found in perilymph of the vestibule, which are higher than would be expected from round window entry alone, undoubtedly contribute to the vestibulotoxic effects of the drug. Furthermore, calculations of gentamicin distribution following targeted applications to the RW or stapes are more consistent with cochleotoxicity depending on the gentamicin concentration in scala vestibuli rather than that in scala tympani. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. The role of preservatives in the conjunctival toxicity of subconjunctival gentamicin injection.

    PubMed Central

    Pande, M.; Ghanchi, F.

    1992-01-01

    Subconjunctival gentamicin was identified as the cause of conjunctival chemosis and capillary closure in a recent study conducted in this department. The gentamicin preparation used in the study contained preservatives. The current prospective study was set up to investigate the role of preservatives in the conjunctival toxicity of subconjunctival gentamicin. Seventy five patients undergoing cataract surgery were enrolled in the study. They were split into three groups of 25 each. Group A patients were given a subconjunctival injection of a preservative-free aqueous solution of gentamicin at the end of the cataract procedure. Group B patients were given a subconjunctival injection of gentamicin containing sodium metabisulphite and disodium edetate as preservatives at the end of the cataract procedure. Group C was the control group where patients were not given any subconjunctival injection. The incidence of severity of conjunctival chemosis were observed in the three groups. The difference between groups A and B patients who received preservative-free gentamicin and gentamicin with preservatives respectively was significant (p < 0.02). PMID:1390493

  12. Pharmacokinetics and therapeutic efficacy of gentamicin in an experimental pleural empyema rabbit model.

    PubMed Central

    Shohet, I; Yellin, A; Meyerovitch, J; Rubinstein, E

    1987-01-01

    The pharmacokinetics and therapeutic efficacy of gentamicin were investigated in an experimental pleural empyema rabbit model. Pleural effusion was induced by the intrapleural administration of turpentine, and empyema was induced by direct inoculation of the effusion with Klebsiella pneumoniae. Pleural empyema compared with effusion was characterized by lower pH, oxygen tension (PaO2), and glucose levels and higher leukocyte count, lactic acid concentration, and PaCO2. After a single administration, gentamicin was first detectable in the pleural fluid at 60 min, whereas peak levels in empyema were observed at 180 min. Gentamicin persisted in the empyema longer than in blood. Animals treated with gentamicin only had 60% bacterial cure on day 7; those treated with gentamicin in an oxygen chamber had 100% cure on day 5 (P = 0.004). Low oxygen tension diminished the antibacterial efficacy of gentamicin in this model. An increase in oxygen tension improved the therapeutic results without alteration of the pharmacokinetics of gentamicin. PMID:3116920

  13. Gentamicin removal in submerged fermentation using the novel fungal strain Aspergillus terreus FZC3

    NASA Astrophysics Data System (ADS)

    Liu, Yuanwang; Chang, Huiqing; Li, Zhaojun; Zhang, Cheng; Feng, Yao; Cheng, Dengmiao

    2016-10-01

    Social concern and awareness of the potential risk posed by environmental residues of antibiotics such as gentamicin in the development of antibiotic resistance genes have increased. The present study used laboratory-scale experiments to develop methods for gentamicin removal from the environment. A fungus, strain FZC3, which could remove gentamicin in submerged fermentation, was isolated from solid waste and sewage water from a gentamicin production factory. The fungus was identified as Aspergillus terreus by sequencing the PCR-amplified ITS fragments of its rRNA-coding genes and by its morphology. The gentamicin removal efficiency exceeded 95% by day 7 under optimized culture conditions. The results showed that both biosorption and biodegradation were involved. We speculated that Aspergillus terreus FZC3 absorbed gentamicin and subsequently degraded it. We also found that Aspergillus terreus FZC3 survived and maintained a high bioremediation efficiency over a wide pH range, indicating its potential for future use in the large-scale bioremediation of gentamicin.

  14. Tetrapeptide-coumarin conjugate 3D networks based on hydrogen-bonded charge transfer complexes: gel formation and dye release.

    PubMed

    Guo, Zongxia; Gong, Ruiying; Jiang, Yi; Wan, Xiaobo

    2015-08-14

    Oligopeptide-based derivatives are important synthons for bio-based functional materials. In this article, a Gly-(L-Val)-Gly-(L-Val)-coumarin (GVGV-Cou) conjugate was synthesized, which forms 3D networks in ethanol. The gel nanostructures were characterized by UV-vis spectroscopy, FT-IR spectroscopy, X-ray diffraction (XRD), SEM and TEM. It is suggested that the formation of charge transfer (CT) complexes between the coumarin moieties is the main driving force for the gel formation. The capability of the gel to encapsulate and release dyes was explored. Both Congo Red (CR) and Methylene Blue (MB) can be trapped in the CT gel matrix and released over time. The present gel might be used as a functional soft material for guest encapsulation and release.

  15. Controlled Release from Core-Shell Nanoporous Silica Particles for Corrosion Inhibition of Aluminum Alloys

    DOE PAGES

    Jiang, Xingmao; Jiang, Ying-Bing; Liu, Nanguo; ...

    2011-01-01

    Ceriumore » m (Ce) corrosion inhibitors were encapsulated into hexagonally ordered nanoporous silica particles via single-step aerosol-assisted self-assembly. The core/shell structured particles are effective for corrosion inhibition of aluminum alloy AA2024-T3. Numerical simulation proved that the core-shell nanostructure delays the release process. The effective diffusion coefficient elucidated from release data for monodisperse particles in water was 1.0 × 10 − 14  m 2 s for Ce 3+ compared to 2.5 × 10 − 13  m 2 s for NaCl. The pore size, pore surface chemistry, and the inhibitor solubility are crucial factors for the application. Microporous hydrophobic particles encapsulating a less soluble corrosion inhibitor are desirable for long-term corrosion inhibition.« less

  16. Novel SERS materials for multiplex biomolecular detection via controlled nanoparticle linking and polymer encapsulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Braun, G B; Lee, S J; Laurence, T

    2008-07-21

    Over the past decade the emphasis on single-molecule sensitivity of surface-enhanced Raman spectroscopy (SERS) has brought to prominence the special role played by so-called SERS 'hot spots', oftentimes nanometer-scale junctions between nanostructures. In this report, optimally SERS enhancing silver clusters were synthesized using bifunctional linkers and polymer and/or protein encapsulation. The synthesis, which results in stable clusters even when stored for months or dried and re-dissolved, is scalable to large quantities. Using a sacrificial linker approach we also employ a permeable polymer/protein shell for general small molecule sensing. Finally, we utilize these nanomaterials by tagging specific epitopes on cancer cellsmore » and show that SERS signals from single clusters can be measured routinely.« less

  17. Industrially prefabricated cement spacers: do vancomycin- and gentamicin-impregnated spacers offer any advantage?

    PubMed

    Corona, Pablo S; Barro, Victor; Mendez, Marye; Cáceres, Enric; Flores, Xavier

    2014-03-01

    Industrially preformed antibiotic-loaded cement spacers are useful to facilitate the second stage of two-stage exchange arthroplasty for infected THAs and TKAs. However, whether gentamicin alone or a combination of antibiotics (such as vancomycin and gentamicin) is more effective is not known. We therefore sought to compare industrially prefabricated spacers containing either gentamicin or gentamicin and vancomycin with respect to (1) infection control, (2) complications, and (3) quality of life, pain, and patient satisfaction. We performed a review of 51 patients with chronic infections treated at one center using either gentamicin or vancomycin and gentamicin-prefabricated spacers. The former were used exclusively from January 2006 until May 2009, and the latter from June 2009 until July 2011, and there was no overlap. We collected data on demographics, immunologic status (McPherson classification), prosthetic joint infection location, type of prosthesis, microbiologic results, and time between stages. We evaluated the primary outcome of infection control or recurrence after at least 12 months followup. We also recorded complications. Each patient completed a quality-of-life survey, VAS, and a self-administered satisfaction scale. The overall infection control rate was 83% after a mean followup of 35 months (range, 12.4-64.7 months). There were no differences between gentamicin and vancomycin and gentamicin spacers in terms of infection eradication (80 % versus 85 %, respectively; p = 0.73), nor in terms of complications, quality of life, pain, or satisfaction scores. Prefabricated, antibiotic-loaded cement spacers has been proven effective for infection control in TKAs and THAs but with the numbers available, we did not find any differences between a gentamicin or vancomycin and gentamicin-prefabricated spacer, and therefore, we are unable to validate the superiority of the combination of vancomycin and gentamicin over gentamicin alone. Because of the higher costs involved with vancomycin and gentamicin spacers, and the potential risks of unselective use of vancomycin, further comparative studies are necessary to evaluate their role in the treatment of infected THAs or TKAs. Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

  18. Time course of apoptotic cell death in guinea pig cochlea following intratympanic gentamicin application.

    PubMed

    Suzuki, Mitsuya; Ushio, Munetaka; Yamasoba, Tatsuya

    2008-07-01

    The present study showed that the molecular signal that promotes the death of cochlear hair cells (HCs) induced by intratympanic gentamicin application is significant before the manifestation of morphological and functional changes. The effect of agents that protect the HCs from aminoglycoside ototoxicity is influenced by the timing of their administration. However, morphological, functional and molecular changes in the cochlea in the early stage following aminoglycoside application have rarely been studied. Therefore, we examined the chronological changes in the cochlea following intratympanic gentamicin application. Small pieces of gelatin sponge soaked with gentamicin (40 mg/ml) were placed on the round window membrane of mature guinea pigs, and the tympanic bulla was filled with gentamicin solution. They were euthanized at 6, 12, 18, 24, and 48 h following gentamicin application. Auditory brainstem responses (ABRs) were measured before gentamicin application and immediately before euthanasia, and the extent of missing and TUNEL-positive HCs was evaluated. ABR thresholds significantly increased 18 h or later following gentamicin application, and the loss of HCs was seen at 24 and 48 h. While functional and morphological changes were not evident until 18 h after gentamicin application, substantial amounts of TUNEL-positive HCs appeared at 12 h.

  19. 21 CFR 524.1044b - Gentamicin sulfate, betamethasone valerate otic solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate, betamethasone valerate otic... NEW ANIMAL DRUGS § 524.1044b Gentamicin sulfate, betamethasone valerate otic solution. (a) Specifications. Each milliliter of solution contains gentamicin sulfate equivalent to 3 milligrams (mg...

  20. 21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 057561...

  1. 21 CFR 524.1044g - Gentamicin sulfate, betamethasone valerate, clotrimazole ointment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate, betamethasone valerate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1044g Gentamicin sulfate, betamethasone valerate, clotrimazole ointment. (a) Specifications. Each gram (g) of ointment contains gentamicin sulfate equivalent to 3...

  2. 21 CFR 524.1044b - Gentamicin sulfate, betamethasone valerate otic solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate, betamethasone valerate otic... NEW ANIMAL DRUGS § 524.1044b Gentamicin sulfate, betamethasone valerate otic solution. (a) Specifications. Each milliliter of solution contains gentamicin sulfate equivalent to 3 milligrams (mg...

  3. 21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 057561...

  4. 21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 057561...

  5. 21 CFR 524.1044g - Gentamicin sulfate, betamethasone valerate, clotrimazole ointment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate, betamethasone valerate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1044g Gentamicin sulfate, betamethasone valerate, clotrimazole ointment. (a) Specifications. Each gram (g) of ointment contains gentamicin sulfate equivalent to 3...

  6. 21 CFR 524.1044g - Gentamicin sulfate, betamethasone valerate, clotrimazole ointment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate, betamethasone valerate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1044g Gentamicin sulfate, betamethasone valerate, clotrimazole ointment. (a) Specifications. Each gram (g) of ointment contains gentamicin sulfate equivalent to 3...

  7. 21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 000859...

  8. 21 CFR 524.1044g - Gentamicin sulfate, betamethasone valerate, clotrimazole ointment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate, betamethasone valerate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1044g Gentamicin sulfate, betamethasone valerate, clotrimazole ointment. (a) Specifications. Each gram (g) of ointment contains gentamicin sulfate equivalent to 3...

  9. Cost evaluation of therapeutic drug monitoring of gentamicin at a teaching hospital in Malaysia

    PubMed Central

    Ibrahim, Mohamed Izham Mohamed; Abdelrahim, Hisham Elhag Ahmed; Ab Rahman, Ab Fatah

    Background Therapeutic drug monitoring (TDM) makes use of serum drug concentrations as an adjunct to decision-making. Preliminary data in our hospital showed that approximately one-fifth of all drugs monitored by TDM service were gentamicin. Objective In this study, we evaluated the costs associated with providing the service in patients with bronchopneumonia and treated with gentamicin. Methods We retrospectively collected data from medical records of patients admitted to the Hospital Universiti Sains Malaysia over a 5-year period. These patients were diagnosed with bronchopneumonia and were on gentamicin as part of their treatment. Five hospitalisation costs were calculated; (i) cost of laboratory and clinical investigations, (ii) cost associated with each gentamicin dose, (iii) fixed and operating costs of TDM service, (iv) cost of providing medical care, and (v) cost of hospital stay during gentamicin treatment. Results There were 1920 patients admitted with bronchopneumonia of which 67 (3.5%) had TDM service for gentamicin. Seventy-three percent (49/67) patients were eligible for final analysis. The duration of gentamicin therapy ranged from 3 to 15 days. The cost of providing one gentamicin assay was MYR25, and the average cost of TDM service for each patient was MYR104. The average total hospitalisation cost during gentamicin treatment for each patient was MYR442 (1EUR approx. MYR4.02). Conclusions Based on the hospital perspective, in patients with bronchopneumonia and treated with gentamicin, the provision of TDM service contributes to less than 25% of the total cost of hospitalization. PMID:24644520

  10. Renal Adaptation to Gentamicin-Induced Mineral Loss

    PubMed Central

    Lee, Chien-Te; Chen, Hung Chun; Ng, Hwee-Yeong; Lai, Li-Wen; Lien, Yeong-Hau H.

    2012-01-01

    Background Gentamicin, a well-known nephrotoxic drug, affects calcium and magnesium homeostasis. Although gentamicin induces urinary calcium and magnesium wasting immediately, it rarely causes significant hypocalcemia or hypomagnesemia clinically. Methods We conducted an animal study to investigate the renal adaptation in calcium and magnesium handling after gentamicin treatment and effects on the expression of calcium and magnesium transport molecules in distal tubule. Gentamicin (40 mg/kg) was injected daily in male Sprague-Dawley rats (220–250 g) for up to 7 days. Results This treatment did not affect serum creatinine, calcium, or magnesium levels. Gentamicin induced significant hypercalciuria (14-fold) and hypermagnesiuria (10-fold) in 6 h, which was associated with upregulation of TRPV5 (175 ± 3%), TRPV6 (170 ± 4%), TRPM6 (156 ± 4%) and calbindin-D28k (174 ± 3%; all p < 0.05 vs. control). This gene upregulation was maintained with daily injection of gentamicin for 7 days. The gentamicin-induced urinary calcium loss was reduced by 80% at days 3 and 7, while magnesium loss was reduced by 52 and 57% at days 3 and 7, respectively. On the other hand, urinary loss of potassium became worse on day 7 (2-fold), and phosphorus loss worse from day 3 to day 7 (3-fold). Conclusion There is a rapid adaptation to gentamicin-induced hypercalciuria and hypermagnesiuria. The upregulation of distal tubule transport molecules, TRPV5, TRPV6, TRPM6 and calbindin-D28k occurs within 6 h of gentamicin treatment. This renal adaptation prevents further mineral loss due to gentamicin treatment. PMID:22378246

  11. Gallium Potentiates the Antibacterial Effect of Gentamicin against Francisella tularensis

    PubMed Central

    Lindgren, Helena

    2015-01-01

    The reasons why aminoglycosides are bactericidal have not been not fully elucidated, and evidence indicates that the cidal effects are at least partly dependent on iron. We demonstrate that availability of iron markedly affects the susceptibility of the facultative intracellular bacterium Francisella tularensis strain SCHU S4 to the aminoglycoside gentamicin. Specifically, the intracellular depots of iron were inversely correlated to gentamicin susceptibility, whereas the extracellular iron concentrations were directly correlated to the susceptibility. Further proof of the intimate link between iron availability and antibiotic susceptibility were the findings that a ΔfslA mutant, which is defective for siderophore-dependent uptake of ferric iron, showed enhanced gentamicin susceptibility and that a ΔfeoB mutant, which is defective for uptake of ferrous iron, displayed complete growth arrest in the presence of gentamicin. Based on the aforementioned findings, it was hypothesized that gallium could potentiate the effect of gentamicin, since gallium is sequestered by iron uptake systems. The ferrozine assay demonstrated that the presence of gallium inhibited >70% of the iron uptake. Addition of gentamicin and/or gallium to infected bone marrow-derived macrophages showed that both 100 μM gallium and 10 μg/ml of gentamicin inhibited intracellular growth of SCHU S4 and that the combined treatment acted synergistically. Moreover, treatment of F. tularensis-infected mice with gentamicin and gallium showed an additive effect. Collectively, the data demonstrate that SCHU S4 is dependent on iron to minimize the effects of gentamicin and that gallium, by inhibiting the iron uptake, potentiates the bactericidal effect of gentamicin in vitro and in vivo. PMID:26503658

  12. Inhibition of gentamicin binding to rat renal brush-border membrane by megalin ligands and basic peptides.

    PubMed

    Nagai, Junya; Saito, Masaki; Adachi, Yoshinori; Yumoto, Ryoko; Takano, Mikihisa

    2006-05-01

    Our previous studies showed that coadministration of cytochrome c and a 20-residue basic peptide, N-WASP181-200 (NISHTKEKKKGKAKKKRLTK, pI=10.87) inhibits renal accumulation of gentamicin. In this study, we examined effects of ligands of megalin, an endocytic receptor involved in renal uptake of gentamicin, and basic peptides including N-WASP180-200 and its mutant peptides on gentamicin binding to isolated rat renal brush-border membrane (BBM). Gentamicin binding to BBM was inhibited by megalin ligands, basic peptide fragments of cytochrome c, and N-WASP181-200 in a concentration-dependent manner. Klotz plot analysis showed that N-WASP181-200 inhibited the binding of gentamicin in a competitive manner. By substituting glycines for lysines in N-WASP181-200 at positions 9 and 15, the inhibitory effect on gentamicin binding to BBM was reduced, which may be related to a decrease in the alpha-helix content in the peptide. Gentamicin binding to BBM treated with trypsin, in which megalin completely disappeared, was significantly but not completely decreased compared with the native BBM. In addition, treatment of BBM with trypsin led to a decrease in the inhibitory effect of N-WASP181-200 on gentamicin binding. These observations support that megalin ligands and basic peptides including N-WASP181-200 decrease renal accumulation of gentamicin by inhibiting its binding to BBM of proximal tubule cells, partly interacting with megalin. In addition, the alpha-helix conformation may play an important role in the inhibitory effect of N-WASP181-200 on the binding of gentamicin to BBM.

  13. 6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

    PubMed

    Hegazy, Ahmed M S; Mosaed, Mohammed M; Elshafey, Saad H; Bayomy, Naglaa A

    2016-06-01

    Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 21 CFR 524.1044h - Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate, mometasone furoate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1044h Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension. (a) Specifications. Each gram contains gentamicin sulfate, United States Pharmacopeia (USP...

  15. 21 CFR 524.1044h - Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate, mometasone furoate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1044h Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension. (a) Specifications. Each gram contains gentamicin sulfate, United States Pharmacopeia (USP...

  16. 21 CFR 524.1044h - Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate, mometasone furoate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1044h Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension. (a) Specifications. Each gram contains gentamicin sulfate, United States Pharmacopeia (USP...

  17. 21 CFR 524.1044h - Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate, mometasone furoate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1044h Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension. (a) Specifications. Each gram contains gentamicin sulfate, United States Pharmacopeia (USP...

  18. Facile synthesis, characterization and magnetic property of CuFe12O19 nanostructures via a sol-gel auto-combustion process

    NASA Astrophysics Data System (ADS)

    Ansari, Fatemeh; Sobhani, Azam; Salavati-Niasari, Masoud

    2016-03-01

    Copper hexaferrite (CuFe12O19) nanostructures were prepared by a simple route utilizing maltose-assisted sol-gel process. The morphology, phase structure, composition and purity of nanostructures can be controlled by type of surfactant and also adjusting the Cu:surfactant, Cu:Fe and Cu:reductant ratios. The bean-shape structures are formed in the absence of the surfactant when the molar ratio of Cu:Fe and Cu:reductant are 1:12 and 1:26, respectively. The agglomerated spherical nanoparticles with diameters ranging from 7 to 20 nm are obtained in the presence of triplex, when ratio of Cu:reductant is 1:26. In the absence of surfactant and also in the presence of triplex, the samples are found to be CuFe12O19. When polymer is used, there are still the peaks of CuFe12O19 and also some boad peaks in XRD patterns, because of the small size and encapsulation of nanostructures with polymer. Magnetic measurments show superparamagnetic behavior for the all samples. The Ms for the samples obtained in the presence of polymer shows that the coating of magnetic nanostructures does not always increase Ms. FT-IR frequency bands in the range 463-626, 607 and 542 cm-1 correspond to the formation of metal oxides in ferrites.

  19. Janus structured Pt–FeNC nanoparticles as a catalyst for the oxygen reduction reaction

    DOE PAGES

    Kuttiyiel, Kurian A.; Sasaki, Kotaro; Park, Gu -Gon; ...

    2017-01-03

    Here, we present a new Janus structured catalyst consisting of Pt nanoparticles on Fe–N–C nanoparticles encapsulated by graphene layers for the ORR. The ORR activity of the catalyst increases under potential cycling as the unique Janus nanostructure is further bonded due to a synergetic effect. The present study describes an important advanced approach for the future design of efficient, stable, and low-cost Pt-based electrocatalytic systems.

  20. Uptake of gentamicin by separated, viable renal tubules from rabbits.

    PubMed

    Barza, M; Murray, T; Hamburger, R J

    1980-04-01

    The proximal renal tubules have a marked affinity for gentamicin; they also are the major site of nephrotoxicity caused by this drug. The uptake of radiolabeled gentamicin in separated, viable renal tubules prepared by enzymatic digestion of rabbit kidneys was studied. The preparations showed rapid initial uptake of gentamicin followed by continued slower uptake. Accumulation was not affected by pH, but was significantly inhibited by ouabain, dinitrophenol, anoxia, and hypothermia in the absence of evident cellular damage. At gentamicin concentrations of greater than 50 microgram/ml in the medium, there was competition for drug uptake. Gentamicin efflux in tubules that were taken from a medium containing antibiotic and placed into antibiotic-free fluid was slow and incomplete. From these data it appears that gentamicin uptake by separated renal tubules occurs by a process that requires metabolic energy; thereafter, the drug resides in a poorly exchangeable cellular pool.

  1. 21 CFR 556.300 - Gentamicin sulfate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate. 556.300 Section 556.300 Food... Tolerances for Residues of New Animal Drugs § 556.300 Gentamicin sulfate. (a) A tolerance of 0.1 part per million is established for negligible residues of gentamicin sulfate in the uncooked edible tissues of...

  2. 21 CFR 556.300 - Gentamicin sulfate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate. 556.300 Section 556.300 Food... Tolerances for Residues of New Animal Drugs § 556.300 Gentamicin sulfate. (a) A tolerance of 0.1 part per million is established for negligible residues of gentamicin sulfate in the uncooked edible tissues of...

  3. 21 CFR 556.300 - Gentamicin sulfate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate. 556.300 Section 556.300 Food... Tolerances for Residues of New Animal Drugs § 556.300 Gentamicin sulfate. (a) A tolerance of 0.1 part per million is established for negligible residues of gentamicin sulfate in the uncooked edible tissues of...

  4. Effect of liquid-to-solid lipid ratio on characterizations of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for transdermal administration.

    PubMed

    Song, Aihua; Zhang, Xiaoshu; Li, Yanting; Mao, Xinjuan; Han, Fei

    2016-08-01

    The aim of this study is to evaluate the effect of liquid-to-solid lipid ratio on properties of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and to clarify the superiority of NLCs over SLNs for transdermal administration. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, differential scanning calorimetry, X-ray diffractometry, in vitro percutaneous permeation profile, and stability of SLNs and NLCs were compared. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, and in vitro percutaneous permeation amount of the developed NLCs were all <200 nm, < -20 mV, >78%, >35, and >240 μg/cm(2), respectively, however, for SLNs were 280 nm, -29.11 mV, 63.2%, 32.54, and 225.9 μg/cm(2), respectively. After 3 months storage at 4 °C and 25 °C, almost no significant differences between the evaluated parameters of NLCs were observed. However, for SLNs, particle size was increased to higher than 300 nm (4 °C and 25 °C), drug encapsulation efficiency was decreased to 51.2 (25 °C), in vitro occlusion factor was also decreased to lower than 25 (4 °C and 25 °C), and the cumulative amount was decreased to 148.9 μg/cm(2) (25 °C) and 184.4 μg/cm(2) (4 °C), respectively. And DSC and XRD studies indicated that not only the crystalline peaks of the encapsulated flurbiprofen disappeared but also obvious difference between samples and bulk Compritol® ATO 888 was seen. It could be concluded that liquid-to-solid lipid ratio has significant impact on the properties of SLNs and NLCs, and NLCs showed better stability than SLNs. Therefore, NLCs might be a better option than SLNs for transdermal administration.

  5. Tauroursodeoxycholic acid attenuates gentamicin-induced cochlear hair cell death in vitro.

    PubMed

    Jia, Zhanwei; He, Qiang; Shan, Chunguang; Li, Fengyi

    2018-09-15

    Gentamycin is one of the most clinically used aminoglycoside antibiotics which induce intrinsic apoptosis of hair cells. Tauroursodeoxycholic acid (TUDCA) is known as safe cell-protective agent in disorders associated with apoptosis. We aimed to investigate the protective effects of TUDCA against gentamicin-induced ototoxicity. House Ear Institute-Organ of Corti 1(HEI-OC1) cells and explanted cochlear tissue were treated with gentamicin and TUDCA, followed by serial analyses including cell viability assay, hair cell staining, qPCR, ELISA and western blotting to determine the cell damage by the parameters relevant to cell apoptosis and endoplasmic reticulum stress. TUDCA significantly attenuated gentamicin-induced cell damage in cultured HEI-OC1 cells and explanted cochlear hair cells. TUDCA alleviated gentamicin-induced cell apoptosis, supported by the decreased Bax/Bcl2 ratio compared with that of gentamicin treated alone. TUDCA decreased gentamicin-induced nitric oxide production and protein nitration in both models. In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Sub-chronic exposure to fluoride impacts the response to a subsequent nephrotoxic treatment with gentamicin.

    PubMed

    Cárdenas-González, Mariana; Jacobo Estrada, Tania; Rodríguez-Muñoz, Rafael; Barrera-Chimal, Jonatan; Bobadilla, Norma A; Barbier, Olivier C; Del Razo, Luz M

    2016-02-01

    Fluoride is an important groundwater contaminant, and more than 200 million people are exposed to high fluoride levels in drinking water, the major source of fluoride exposure. Exposure above 2 ppm of fluoride is associated with renal impairment in humans. In rats, moderate levels of fluoride induce kidney injury at early stages in which the glomerular filtration rate (GFR) is not altered. In the present study, we investigated if sub-nephrotoxic stimulus induced by fluoride might impact the response to a subsequent nephrotoxic treatment with gentamicin. Male Wistar rats (~21 days) were exposed to 0, 15 or 50 ppm of fluoride through drinking water during 40 days. Afer that, rats were co-exposed to gentamicin (40 mg kg(-1) day(-1), 7 days). Gentamicin induced a marked decrease in the GFR and an increase in urinary levels as well as the protein and mRNA expression of biomarkers of early kidney injury, such as Kim-1. Interestingly, gentamicin nephrotoxicity was less pronounced in groups previously exposed to fluoride than in the group only treated with gentamicin. Fluoride induced Hsp72, a cytoprotective molecule, which might have improved the response against gentamicin. Moreover, fluoride decreased the expression of megalin, a molecule necessary for internalization of gentamicin into the proximal tubule, potentially reducing gentamicin accumulation. The present results suggest that fluoride reduced gentamicin-induced nephrotoxicity by inducing a compensatory response carried out by Hsp72 and by decreasing gentamicin accumulation. These findings should not be interpreted to suggest that fluoride is a protective agent as megalin deficiency could lead to serious adverse effects on the kidney physiology. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients

    PubMed Central

    Woodley, David T.; Cogan, Jon; Hou, Yingping; Lyu, Chao; Marinkovich, M. Peter; Keene, Douglas

    2017-01-01

    BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease caused by mutations in the gene encoding type VII collagen, the major component of anchoring fibrils (AF). We previously demonstrated that gentamicin produced functional type VII collagen in RDEB cells harboring nonsense mutations. Herein, we determined whether topical or intradermal gentamicin administration induces type VII collagen and AFs in RDEB patients. METHODS. A double-blind, placebo-controlled pilot trial assessed safety and efficacy of topical and intradermal gentamicin in 5 RDEB patients with nonsense mutations. The topical arm tested 0.1% gentamicin ointment or placebo application 3 times daily at 2 open erosion sites for 2 weeks. The intradermal arm tested daily intradermal injection of gentamicin solution (8 mg) or placebo into 2 intact skin sites for 2 days in 4 of 5 patients. Primary outcomes were induction of type VII collagen and AFs at the test sites and safety assessment. A secondary outcome assessed wound closure of topically treated erosions. RESULTS. Both topical and intradermal gentamicin administration induced type VII collagen and AFs at the dermal-epidermal junction of treatment sites. Newly created type VII collagen varied from 20% to 165% of that expressed in normal human skin and persisted for 3 months. Topical gentamicin corrected dermal-epidermal separation, improved wound closure, and reduced blister formation. There were no untoward side effects from gentamicin treatments. Type VII collagen induction did not generate anti–type VII collagen autoantibodies in patients’ blood or skin. CONCLUSION. Topical and intradermal gentamicin suppresses nonsense mutations and induces type VII collagen and AFs in RDEB patients. Gentamicin therapy may provide a readily available treatment for RDEB patients with nonsense mutations. TRIAL REGISTRATION. ClinicalTrials.gov NCT02698735. FUNDING. Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH, and VA Merit Award. PMID:28691931

  8. Gallium Potentiates the Antibacterial Effect of Gentamicin against Francisella tularensis.

    PubMed

    Lindgren, Helena; Sjöstedt, Anders

    2016-01-01

    The reasons why aminoglycosides are bactericidal have not been not fully elucidated, and evidence indicates that the cidal effects are at least partly dependent on iron. We demonstrate that availability of iron markedly affects the susceptibility of the facultative intracellular bacterium Francisella tularensis strain SCHU S4 to the aminoglycoside gentamicin. Specifically, the intracellular depots of iron were inversely correlated to gentamicin susceptibility, whereas the extracellular iron concentrations were directly correlated to the susceptibility. Further proof of the intimate link between iron availability and antibiotic susceptibility were the findings that a ΔfslA mutant, which is defective for siderophore-dependent uptake of ferric iron, showed enhanced gentamicin susceptibility and that a ΔfeoB mutant, which is defective for uptake of ferrous iron, displayed complete growth arrest in the presence of gentamicin. Based on the aforementioned findings, it was hypothesized that gallium could potentiate the effect of gentamicin, since gallium is sequestered by iron uptake systems. The ferrozine assay demonstrated that the presence of gallium inhibited >70% of the iron uptake. Addition of gentamicin and/or gallium to infected bone marrow-derived macrophages showed that both 100 μM gallium and 10 μg/ml of gentamicin inhibited intracellular growth of SCHU S4 and that the combined treatment acted synergistically. Moreover, treatment of F. tularensis-infected mice with gentamicin and gallium showed an additive effect. Collectively, the data demonstrate that SCHU S4 is dependent on iron to minimize the effects of gentamicin and that gallium, by inhibiting the iron uptake, potentiates the bactericidal effect of gentamicin in vitro and in vivo. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Prevention of gentamicin-induced apoptosis with the mitochondria-targeted antioxidant mitoquinone.

    PubMed

    Ojano-Dirain, Carolyn P; Antonelli, Patrick J

    2012-11-01

    Antioxidants have been shown to protect against aminoglycoside-induced hearing loss. Mitoquinone (MitoQ) is a mitochondria-targeted derivative of the antioxidant ubiquinone. MitoQ is attached to a lipophilic triphenylphosphonium (TPP) cation, which enables its accumulation inside the mitochondria several hundred-fold over the untargeted antioxidant. The goals of this study were to determine if MitoQ attenuates gentamicin-induced activation of caspase-3/7 activity as a marker of apoptosis and to determine if MitoQ impacts aminoglycoside antimicrobial efficacy. Prospective and controlled. Antibiotic efficacy and minimum inhibitory concentrations (MICs) of gentamicin against three strains each of Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa were evaluated with and without MitoQ using broth dilution methods. Apoptosis was assessed by caspase-3/7 activity in untreated HEI-OC1 cells and cells exposed to 2 mM gentamicin for 24 hours, with and without a 24-hour preincubation with 0.5 μM each of MitoQ, idebenone (an untargeted ubiquinone), or decylTPP (positive control). Gentamicin MICs for P aeruginosa and H influenzae were not affected by MitoQ at pharmacological levels. MICs for S aureus were enhanced by MitoQ. Cell viability was significantly lower in the gentamicin-treated cells. A significant increase in caspase-3/7 activity was observed in cells treated with gentamicin or with idebenone + gentamicin (P = .005). Preincubation with MitoQ decreased the gentamicin-induced apoptosis of HEI-OC1 cells to a greater extent compared to idebenone (P = .002). MitoQ attenuates gentamicin-induced apoptosis in HEI-OC1 cells and does not compromise gentamicin antibiotic efficacy. MitoQ holds promise as a means of preventing aminoglycoside ototoxicity. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  10. Effects of gentamicin and gentamicin-RGD coatings on bone ingrowth and biocompatibility of cementless joint prostheses: an experimental study in rabbits.

    PubMed

    Alt, Volker; Bitschnau, Achim; Böhner, Felicitas; Heerich, Katharina Elisabeth; Magesin, Erika; Sewing, Andreas; Pavlidis, Theodoros; Szalay, Gabor; Heiss, Christian; Thormann, Ulrich; Hartmann, Sonja; Pabst, Wolfgang; Wenisch, Sabine; Schnettler, Reinhard

    2011-03-01

    Antimicrobial coatings are of interest as a means to improve infection prophylaxis in cementless joint arthroplasty. However, those coatings must not interfere with the essential bony integration of the implants. Gentamicin-hydroxyapatite (gentamicin-HA) and gentamicin-RGD (arginine-glycine-aspartate)-HA coatings have recently been shown to significantly reduce infection rates in a rabbit infection prophylaxis model. The purpose of the current study was to investigate the in vitro elution kinetics and in vivo effects of gentamicin-HA and gentamicin-RGD-HA coatings on new bone formation, implant integration and biocompatibility in a rabbit model. In vitro elution testing showed that 95% and 99% of the gentamicin was released after 12 and 24 h, respectively. The in vivo study comprised 45 rabbits in total, with six animals for each of the gentamicin-HA, gentamicin-RGD-HA group and control pure HA coating groups for the 4 week time period, and nine animals for each of the three groups for the 12 week observation period. A 2.0 mm steel K-wire with one of the coatings under test was placed in the intramedullary canal of the tibia. After 4 and 12 weeks the tibiae were harvested and three different areas (proximal metaphysis, shaft area, distal metaphysis) were assessed by quantitative and qualitative histology for new bone formation, direct implant-bone contact and the formation of multinucleated giant cells. The results exhibited high standard deviations in all subgroups. There was a trend towards better bone formation and better direct implant contact in the pure HA coating group compared with both gentamicin coatings after 4 and 12 weeks, which was, however, not statistically significant. The number of multinucleated giant cells did not differ significantly between the three groups at both time points. In summary, both gentamicin coatings with 99% release of gentamicin within 24 h revealed good biocompatibility and bony integration, which was not statistically significant different compared with pure HA coating. Limitations of the study are the high standard deviation of the results and the limited number of animals per time point. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  11. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrialmore » NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney. - Highlights: • Naringin ameliorated gentamicin-induced nephrotoxicity in rats. • Naringin treatment attenuated gentamicin-induced renal apoptosis in rats. • Naringin ameliorated gentamicin-induced renal mitochondrial dysfunction in rats. • Naringin decreased NF-κB activation and pro-inflammatory cytokine release. • U-HPLC-MS data revealed that naringin did not alter the renal uptake of gentamicin.« less

  12. Encapsulation of Aconitine in Self-Assembled Licorice Protein Nanoparticles Reduces the Toxicity In Vivo

    NASA Astrophysics Data System (ADS)

    Ke, Li-jing; Gao, Guan-zhen; Shen, Yong; Zhou, Jian-wu; Rao, Ping-fan

    2015-11-01

    Many herbal medicines and compositions are clinically effective but challenged by its safety risks, i.e., aconitine (AC) from aconite species. The combined use of Radix glycyrrhizae (licorice) with Radix aconite L. effectively eliminates toxicity of the later while increasing efficacy. In this study, a boiling-stable 31-kDa protein (namely GP) was purified from licorice and self-assembled into nanoparticles (206.2 ± 2.0 nm) at pH 5.0, 25 °C. The aconitine-encapsulated GP nanoparticles (238.2 ± 1.2 nm) were prepared following the same procedure and tested for its toxicity by intraperitoneal injection on ICR mouse ( n = 8). Injection of GP-AC nanoparticles and the mixed licorice-aconite decoction, respectively, caused mild recoverable toxic effects and no death, while the aconitine, particle-free GP-AC mixture and aconite decoction induced sever toxic effects and 100 % death. Encapsulation of poisonous alkaloids into self-assembled herbal protein nanoparticles contributes to toxicity attenuation of combined use of herbs, implying a prototype nanostructure and a universal principle for the safer clinical applications of herbal medicines.

  13. Nanotechnology: current uses and future applications in the food industry.

    PubMed

    Thiruvengadam, Muthu; Rajakumar, Govindasamy; Chung, Ill-Min

    2018-01-01

    Recent advances in nanoscience and nanotechnology intend new and innovative applications in the food industry. Nanotechnology exposed to be an efficient method in many fields, particularly the food industry and the area of functional foods. Though as is the circumstance with the growth of any novel food processing technology, food packaging material, or food ingredient, additional studies are needed to demonstrate the potential benefits of nanotechnologies and engineered nanomaterials designed for use in foods without adverse health effects. Nanoemulsions display numerous advantages over conventional emulsions due to the small droplets size they contain: high optical clarity, excellent physical constancy against gravitational partition and droplet accumulation, and improved bioavailability of encapsulated materials, which make them suitable for food applications. Nano-encapsulation is the most significant favorable technologies having the possibility to ensnare bioactive chemicals. This review highlights the applications of current nanotechnology research in food technology and agriculture, including nanoemulsion, nanocomposites, nanosensors, nano-encapsulation, food packaging, and propose future developments in the developing field of agrifood nanotechnology. Also, an overview of nanostructured materials, and their current applications and future perspectives in food science are also presented.

  14. Comparison of gentamicin and kanamycin alone and in combination with ampicillin in experimental Escherichia coli bacteremia and meningitis.

    PubMed

    Kim, K S

    1985-11-01

    The conventional antimicrobial therapy of gram-negative infection in the newborn is the combination of ampicillin and an aminoglycoside, usually gentamicin or kanamycin. Although gentamicin and kanamycin have been used interchangeably, efficacies of the two drugs have not been carefully compared. In addition, the contribution of ampicillin to the outcome of neonatal gram-negative meningitis is controversial. We evaluated the activity of gentamicin and kanamycin alone and in combinations with ampicillin in vitro and in vivo against a K1 Escherichia coli strain. In vitro, the E. coli strain was relatively sensitive to ampicillin, gentamicin, and kanamycin, with the minimal inhibitory and minimal bactericidal concentrations of 2 and 4, 2 and 2, and 4 and 8 micrograms/ml, respectively. Checkerboard determinations of minimal inhibitory and minimal bactericidal concentrations of drug combinations exhibited an indifferent response for both ampicillin + gentamicin and ampicillin + kanamycin. However, in vivo studies using an experimental E. coli bacteremia and meningitis model in newborn rats suggested that gentamicin was more effective than kanamycin. This was shown by more rapid bacterial clearance from the blood, a decreased incidence of meningitis in bacteremic animals, and improved survival. Furthermore, the addition of ampicillin improved the outcome of kanamycin, but not gentamicin, suggesting that the contribution of ampicillin may vary depending on the type of aminoglycoside used. These findings suggest that kanamycin is less effective than gentamicin in vivo against E. coli and should be used in combination with ampicillin to achieve an outcome comparable to that of gentamicin in this model of E. coli infection.

  15. Subcellular mechanisms involved in apoptosis induced by aminoglycoside antibiotics: Insights on p53, proteasome and endoplasmic reticulum

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Denamur, Sophie; Boland, Lidvine

    Gentamicin, an aminoglycoside used to treat severe bacterial infections, may cause acute renal failure. In the renal cell line LLC-PK1, gentamicin accumulates in lysosomes, induces alterations of their permeability, and triggers the mitochondrial pathway of apoptosis via activation of caspase-9 and -3 and changes in Bcl-2 family proteins. Early ROS production in lysosomes has been associated with gentamicin induced lysosomal membrane permeabilization. In order to better understand the multiple interconnected pathways of gentamicin-induced apoptosis and ensuing renal cell toxicity, we investigated the effect of gentamicin on p53 and p21 levels. We also studied the potential effect of gentamicin on proteasomemore » by measuring the chymotrypsin-, trypsin- and caspase-like activities, and on endoplasmic reticulum by determining phopho-eIF2α, caspase-12 activation and GRP78 and 94. We observed an increase in p53 levels, which was dependent on ROS production. Accumulation of p53 resulted in accumulation of p21 and of phospho-eIF2α. These effects could be related to an impairment of proteasome as we demonstrated an inhibition of trypsin-and caspase-like activities. Moderate endoplasmic reticulum stress could also participate to cellular toxicity induced by gentamicin, with activation of caspase-12 without change in GRP74 and GRP98. All together, these data provide new mechanistic insights into the apoptosis induced by aminoglycoside antibiotics on renal cell lines. - Highlights: • Gentamicin induces apoptosis through p53 pathway. • Gentamicin inhibits proteosomal activity. • Gentamicin activates caspase-12.« less

  16. A droplet-based heterogeneous immunoassay for screening single cells secreting antigen-specific antibodies.

    PubMed

    Akbari, Samin; Pirbodaghi, Tohid

    2014-09-07

    High throughput heterogeneous immunoassays that screen antigen-specific antibody secreting cells are essential to accelerate monoclonal antibody discovery for therapeutic applications. Here, we introduce a heterogeneous single cell immunoassay based on alginate microparticles as permeable cell culture chambers. Using a microfluidic device, we encapsulated single antibody secreting cells in 35-40 μm diameter alginate microbeads. We functionalized the alginate to capture the secreted antibodies inside the microparticles, enabling single cell analysis and preventing the cross-talk between the neighboring encapsulated cells. We demonstrated non-covalent functionalization of alginate microparticles by adding three secondary antibodies to the alginate solution to form high molecular weight complexes that become trapped in the porous nanostructure of alginate and capture the secreted antibodies. We screened anti-TNF-alpha antibody-secreting cells from a mixture of antibody-secreting cells.

  17. Generating a heated fluid using an electromagnetic radiation-absorbing complex

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Halas, Nancy J.; Nordlander, Peter; Neumann, Oara

    A vessel including a concentrator configured to concentrate electromagnetic (EM) radiation received from an EM radiation source and a complex configured to absorb EM radiation to generate heat. The vessel is configured to receive a cool fluid from the cool fluid source, concentrate the EM radiation using the concentrator, apply the EM radiation to the complex, and transform, using the heat generated by the complex, the cool fluid to the heated fluid. The complex is at least one of consisting of copper nanoparticles, copper oxide nanoparticles, nanoshells, nanorods, carbon moieties, encapsulated nanoshells, encapsulated nanoparticles, and branched nanostructures. Further, the EMmore » radiation is at least one of EM radiation in an ultraviolet region of an electromagnetic spectrum, in a visible region of the electromagnetic spectrum, and in an infrared region of the electromagnetic spectrum.« less

  18. Dendrimer-encapsulated nanoparticle-core micelles as a modular strategy for particle-in-a-box-in-a-box nanostructures.

    PubMed

    Ten Hove, J B; Wang, J; van Leeuwen, F W B; Velders, A H

    2017-12-07

    The hierarchically controlled synthesis and characterization of self-assembling macromolecules and particles are key to explore and exploit new nanomaterials. Here we present a versatile strategy for constructing particle-in-a-box-in-a-box systems by assembling dendrimer-encapsulated gold nanoparticles (DENs) into dendrimicelles. This is realized by combining positively charged PAMAM dendrimers with a negative-neutral block copolymer. The number of particles per dendrimicelle can be controlled by mixing DENs with empty PAMAM dendrimers. The dendrimicelles are stable in solution for months and provide improved resistance for the nanoparticles against degradation. The dendrimicelle strategy provides a flexible platform with a plethora of options for variation in the type of nanoparticles, dendrimers and block copolymers used, and hence is tunable for applications ranging from nanomedicine to catalysis.

  19. Hydrophobic Drug Encapsulation Mechanisms of an Injectable Self-Assembling Peptide Hydrogel

    NASA Astrophysics Data System (ADS)

    Sun, Jessie E. P.; Schneider, Joel P.; Pochan, Darrin J.

    2012-02-01

    We examined a beta-hairpin peptide network that is a shear thinning injectable solid with immediate rehealing behavior. These rheological properties result from the entangled and branched fibrillar nanostructure of the hydrogel networks. The fibrils are formed by the intramolecular folding and subsequent intermolecular assembly of the self-assembling peptides. Taking advantage of the nanofibrillar peptide structures, the hydrogel can be used to encapsulate curcumin, a hydrophobic, natural anticancer agent and indian spice. The hydrogel shields curcumin from the environment while depositing it exactly where it is intended through syringe injection, taking advantage of the hydrogel shear thinning and rehealing behavior. How the network envelopes and interacts with the curcumin is examined using fluoresence and electron microscopy methods to better understand the exact mechanisms and behaviors of the gel itself and the gel-curcumin construct.

  20. Gentamicin Binds to the Megalin Receptor as a Competitive Inhibitor Using the Common Ligand Binding Motif of Complement Type Repeats

    PubMed Central

    Dagil, Robert; O'Shea, Charlotte; Nykjær, Anders; Bonvin, Alexandre M. J. J.; Kragelund, Birthe B.

    2013-01-01

    Gentamicin is an aminoglycoside widely used in treatments of, in particular, enterococcal, mycobacterial, and severe Gram-negative bacterial infections. Large doses of gentamicin cause nephrotoxicity and ototoxicity, entering the cell via the receptor megalin. Until now, no structural information has been available to describe the interaction with gentamicin in atomic detail, and neither have any three-dimensional structures of domains from the human megalin receptor been solved. To address this gap in our knowledge, we have solved the NMR structure of the 10th complement type repeat of human megalin and investigated its interaction with gentamicin. Using NMR titration data in HADDOCK, we have generated a three-dimensional model describing the complex between megalin and gentamicin. Gentamicin binds to megalin with low affinity and exploits the common ligand binding motif previously described (Jensen, G. A., Andersen, O. M., Bonvin, A. M., Bjerrum-Bohr, I., Etzerodt, M., Thogersen, H. C., O'Shea, C., Poulsen, F. M., and Kragelund, B. B. (2006) J. Mol. Biol. 362, 700–716) utilizing the indole side chain of Trp-1126 and the negatively charged residues Asp-1129, Asp-1131, and Asp-1133. Binding to megalin is highly similar to gentamicin binding to calreticulin. We discuss the impact of this novel insight for the future structure-based design of gentamicin antagonists. PMID:23275343

  1. Safety of gentamicin bladder irrigations in complex urological cases.

    PubMed

    Defoor, William; Ferguson, Denise; Mashni, Susan; Creelman, Lisa; Reeves, Deborah; Minevich, Eugene; Reddy, Pramod; Sheldon, Curtis

    2006-05-01

    Recurrent urinary tract infections are common in complex pediatric urological cases, particularly those requiring clean intermittent catheterization. At our institution gentamicin bladder irrigations have been used for antimicrobial prophylaxis and to treat symptomatic bacteriuria, particularly when the infection does not involve the upper urinary tract. The purpose of this study was to assess the safety of this therapy. A retrospective study was performed of all children treated with gentamicin bladder irrigations from 1999 to 2004. The dose was 14 mg gentamicin in 30 ml saline instilled via catheter once or twice daily. Serum creatinine and random gentamicin levels were obtained according to a protocol based on risk of gentamicin toxicity. Patient demographics, laboratory results and outcomes were abstracted from the medical records. A total of 80 patients (38 males and 42 females) were identified. Median patient age was 10 years and median duration of treatment was 90 days. No patient had detectable serum gentamicin levels greater than 0.4 mg/dl. Small increases in serum creatinine were seen in 3 patients, all of whom had chronic renal insufficiency. A total of 21 patients (26%) had breakthrough UTIs, of which 5 (24%) were gentamicin resistant. No adverse events were documented. Gentamicin bladder irrigations are a helpful adjunct in the management of complex pediatric urological cases involving recurrent symptomatic bacteriuria. We no longer require intensive laboratory monitoring of low risk patients at our institution.

  2. Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants

    PubMed Central

    Fuchs, Aline; Zimmermann, Lara; Bickle Graz, Myriam; Cherpillod, Jacques; Tolsa, Jean-François; Buclin, Thierry; Giannoni, Eric

    2016-01-01

    Objective To evaluate the impact of gentamicin exposure on sensorineural hearing loss (SNHL) in very low birth weight (VLBW) infants. Methods Exposure to gentamicin was determined in infants born between 1993 and 2010 at a gestational age < 32 weeks and/or with a birthweight < 1500 g, who presented with SNHL during the first 5 years of life. For each case, we selected two controls matched for gender, gestational age, birthweight, and year of birth. Results We identified 25 infants affected by SNHL, leading to an incidence of SNHL of 1.58% in our population of VLBW infants. The proportion of infants treated with gentamicin was 76% in the study group and 70% in controls (p = 0.78). The total cumulated dose of gentamicin administered did not differ between the study group (median 10.2 mg/kg, Q1-Q3 1.6–13.2) and the control group (median 7.9 mg/kg, Q1-Q3 0–12.8, p = 0.47). The median duration of gentamicin treatment was 3 days both in the study group and the control group (p = 0.58). Maximum predicted trough serum levels of gentamicin, cumulative area under the curve and gentamicin clearance were not different between cases and controls. Conclusion The impact of gentamicin on SNHL can be minimized with treatments of short duration, monitoring of blood levels and dose adjustment. PMID:27390846

  3. Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants.

    PubMed

    Fuchs, Aline; Zimmermann, Lara; Bickle Graz, Myriam; Cherpillod, Jacques; Tolsa, Jean-François; Buclin, Thierry; Giannoni, Eric

    2016-01-01

    To evaluate the impact of gentamicin exposure on sensorineural hearing loss (SNHL) in very low birth weight (VLBW) infants. Exposure to gentamicin was determined in infants born between 1993 and 2010 at a gestational age < 32 weeks and/or with a birthweight < 1500 g, who presented with SNHL during the first 5 years of life. For each case, we selected two controls matched for gender, gestational age, birthweight, and year of birth. We identified 25 infants affected by SNHL, leading to an incidence of SNHL of 1.58% in our population of VLBW infants. The proportion of infants treated with gentamicin was 76% in the study group and 70% in controls (p = 0.78). The total cumulated dose of gentamicin administered did not differ between the study group (median 10.2 mg/kg, Q1-Q3 1.6-13.2) and the control group (median 7.9 mg/kg, Q1-Q3 0-12.8, p = 0.47). The median duration of gentamicin treatment was 3 days both in the study group and the control group (p = 0.58). Maximum predicted trough serum levels of gentamicin, cumulative area under the curve and gentamicin clearance were not different between cases and controls. The impact of gentamicin on SNHL can be minimized with treatments of short duration, monitoring of blood levels and dose adjustment.

  4. Rational Design of Hierarchical Nanotubes through Encapsulating CoSe2 Nanoparticles into MoSe2/C Composite Shells with Enhanced Lithium and Sodium Storage Performance.

    PubMed

    Gao, Jingyu; Li, Yapeng; Shi, Liang; Li, Jingjing; Zhang, Genqiang

    2018-06-20

    Transition-metal diselenides have been extensively studied as desirable anode candidates for both lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) because of their high theoretical capacities. However, it is of great challenge to achieve satisfactory cycling performance, especially for larger sodium ion storage, originated from electrode deterioration upon large volume change. Herein, we reported the construction of hierarchical tubular hybrid nanostructures through encapsulating CoSe 2 nanoparticles into MoSe 2 /C composite shells via a simple two-step strategy including a hydrothermal method followed by vapor-phase selenization process. The unique tubular structure enables the highly reversible Li/Na storage with high specific capacity, enhanced cycling stability, and superior rate performance. It is indicated that the contribution of partial pseudocapacitive behavior greatly improves the rate capability for SIBs, where a high capacity retention of 81.5% can be obtained when the current densities range from 0.1 to 3 A g -1 (460 mA h g -1 at 0.1 A g -1 vs 379 mA h g -1 at 3 A g -1 ). This work provides an effective design rationale on transition-metal diselenide-based tubular nanostructures as superior hosts for both Li and Na ions, which could push forward the development of practical applications of transition-metal diselenide-based anodes in LIBs and SIBs.

  5. Improvement of citral antimicrobial activity by incorporation into nanostructured lipid carriers: a potential application in food stuffs as a natural preservative.

    PubMed

    Mokarizadeh, Manijeh; Kafil, Hossein Samadi; Ghanbarzadeh, Saeed; Alizadeh, Ainaz; Hamishehkar, Hamed

    2017-10-01

    At the present time, utilization of essential oils in food preservation to prevent bacterial and fungal growth and improve shelf life and safety of the food products has notably gained increased interest. The aim of the present study was to improve the antimicrobial efficacy of citral as a natural preservative using nanostructured lipid carriers (NLCs). Formulations of NLCs were characterized using particle size analysis and scanning electron microscopy methods. Possible citral-carrier interaction and citral encapsulation efficiency percent (EE%) were assessed by Fourier transform infrared (FTIR) spectroscopy and gas chromatography techniques, respectively. Antimicrobial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of citral-loaded NLCs were evaluated and compared with the conventional citral emulsion against various gram-positive bacteria ( Staphylococcus aureus , Bacillus cereus ), gram-negative bacteria ( Escherichia coli ), and fungi ( Candida albicans ). Citral-loaded NLCs were spherically shaped nanosized (74.8 nm) particles with narrow size distribution, high EE% (99.84%), and appropriate physical stability during 90 days of storage period. FTIR spectra indicated the interaction between citral and formulation ingredients, which justified the obtained high EE% value. The MIC and MBC values of citral-loaded NLCs were lower than those of citral emulsion for all microorganisms. NLCs formulation showed remarkable capability of encapsulating essential oil and increasing antimicrobial properties to offer effective preservation in food industry.

  6. Inhibition of caspases alleviates gentamicin-induced cochlear damage in guinea pigs.

    PubMed

    Okuda, Takeshi; Sugahara, Kazuma; Takemoto, Tsuyoshi; Shimogori, Hiroaki; Yamashita, Hiroshi

    2005-03-01

    The efficacy of caspase inhibitors for protecting the cochlea was evaluated in an in vivo study using guinea pigs, as the animal model system. Gentamicin (12 mg/ml) was delivered via an osmotic pump into the cochlear perilymphatic space of guinea pigs at 0.5 microl/h for 14 days. Additional animals were given either z-Val-Ala-Asp (Ome)-fluoromethyl ketone (z-VAD-FMK) or z-Leu-Glu-His-Asp-FMK (z-LEHD-FMK), a general caspase inhibitor and a caspase 9 inhibitor, respectively, in addition to gentamicin. The elevation in auditory brain stem response thresholds, at 4, 7, and 14 days following gentamicin administration, were decreased in animals that received both z-VAD-FMK and z-LEHD-FMK. Cochlear sensory hair cells survived in greater numbers in animals that received caspase inhibitors in addition to gentamicin, whereas sensory hair cells in animals that received gentamicin only were severely damaged. These results suggest that auditory cell death induced by gentamicin is closely related to the activation of caspases in vivo.

  7. 21 CFR 862.3450 - Gentamicin test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862... in the diagnosis and treatment of gentamicin overdose and in monitoring levels of gentamicin to...

  8. [Multicenter study comparing the efficacy and tolerance of topical ciprofloxacin (0.3%) versus topical gentamicin (0.3%) in the treatment of simple, non-cholesteatomaous chronic otitis media in the suppurative phase].

    PubMed

    Lorente, J; Sabater, F; Maristany, M; Jiménez, R; Menem, J; Viñas, J; Quesada, P; Traserra, J; Dicenta, M; Abelló, P

    1995-01-01

    A multicentre double-blind randomized study was carried out to compare topical ciprofloxacin and topical gentamicin in the treatment of simple non-cholesteatomatous purulent chronic otitis media. Three hundred and eight patients were included in the study, 159 treated with ciprofloxacin and 149 treated with gentamicin. The percentage of clinical success (elimination of otorrhoea) was 95% with ciprofloxacin and 94% with gentamicin (ns). Likewise, the percentage of bacteriological erradication was 96% with ciprofloxacin and 93% with gentamicin. Both drugs were well tolerated, without changes in the audiometric values. In these patients, topical ciprofloxacin shows the same efficacy as topical gentamicin without any potential ototoxic effect.

  9. Confined Assembly of Hollow Carbon Spheres in Carbonaceous Nanotube: A Spheres-in-Tube Carbon Nanostructure with Hierarchical Porosity for High-Performance Supercapacitor.

    PubMed

    Chen, Ze; Ye, Sunjie; Evans, Stephen D; Ge, Yuanhang; Zhu, Zhifeng; Tu, Yingfeng; Yang, Xiaoming

    2018-05-01

    Carbonaceous nanotubes (CTs) represent one of the most popular and effective carbon electrode materials for supercapacitors, but the electrochemistry performance of CTs is largely limited by their relatively low specific surface area, insufficient usage of intratube cavity, low content of heteroatom, and poor porosity. An emerging strategy for circumventing these issues is to design novel porous CT-based nanostructures. Herein, a spheres-in-tube nanostructure with hierarchical porosity is successfully engineered, by encapsulating heteroatom-doping hollow carbon spheres into one carbonaceous nanotube (HCSs@CT). This intriguing nanoarchitecture integrates the merits of large specific surface area, good porosity, and high content of heteroatoms, which synergistically facilitates the transportation and exchange of ions and electrons. Accordingly, the as-prepared HCSs@CTs possess outstanding performances as electrode materials of supercapacitors, including superior capacitance to that of CTs, HCSs, and their mixtures, coupled with excellent cycling life, demonstrating great potential for applications in energy storage. © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Lyotropic liquid crystal engineering moving beyond binary compositional space - ordered nanostructured amphiphile self-assembly materials by design.

    PubMed

    van 't Hag, Leonie; Gras, Sally L; Conn, Charlotte E; Drummond, Calum J

    2017-05-22

    Ordered amphiphile self-assembly materials with a tunable three-dimensional (3D) nanostructure are of fundamental interest, and crucial for progressing several biological and biomedical applications, including in meso membrane protein crystallization, as drug and medical contrast agent delivery vehicles, and as biosensors and biofuel cells. In binary systems consisting of an amphiphile and a solvent, the ability to tune the 3D cubic phase nanostructure, lipid bilayer properties and the lipid mesophase is limited. A move beyond the binary compositional space is therefore required for efficient engineering of the required material properties. In this critical review, the phase transitions upon encapsulation of more than 130 amphiphilic and soluble additives into the bicontinuous lipidic cubic phase under excess hydration are summarized. The data are interpreted using geometric considerations, interfacial curvature, electrostatic interactions, partition coefficients and miscibility of the alkyl chains. The obtained lyotropic liquid crystal engineering design rules can be used to enhance the formulation of self-assembly materials and provides a large library of these materials for use in biomedical applications (242 references).

  11. Effects of silica–gentamicin nanohybrids on osteogenic differentiation of human osteoblast-like SaOS-2 cells

    PubMed Central

    He, Wei; Mosselhy, Dina A; Li, Xiaoning; Yang, Xing; Yue, Lina; Hannula, Simo-Pekka

    2018-01-01

    Introduction In recent years, there has been an increasing interest in silica (SiO2) nanoparticles (NPs) as drug delivery systems. This interest is mainly attributed to the ease of their surface functionalization for drug loading. In orthopedic applications, gentamicin-loaded SiO2 NPs (nanohybrids) are frequently utilized for their prolonged antibacterial effects. Therefore, the possible adverse effects of SiO2–gentamicin nanohybrids on osteogenesis of bone-related cells should be thoroughly investigated to ensure safe applications. Materials and methods The effects of SiO2–gentamicin nanohybrids on the cell viability and osteogenic differentiation of human osteoblast-like SaOS-2 cells were investigated, together with native SiO2 NPs and free gentamicin. Results The results of Cell Count Kit-8 (CCK-8) assay show that both SiO2–gentamicin nanohybrids and native SiO2 NPs reduce cell viability of SaOS-2 cells in a dose-dependent manner. Regarding osteogenesis, SiO2–gentamicin nanohybrids and native SiO2 NPs at the concentration range of 31.25–125 μg/mL do not influence the osteogenic differentiation capacity of SaOS-2 cells. At a high concentration (250 μg/mL), both materials induce a lower expression of alkaline phosphatase (ALP) but an enhanced mineralization. Free gentamicin at concentrations of 6.26 and 9.65 μg/mL does not significantly influence the cell viability and osteogenic differentiation capacity of SaOS-2 cells. Conclusions The results of this study suggest that both SiO2–gentamicin nanohybrids and SiO2 NPs show cytotoxic effects to SaOS-2 cells. Further investigation on the effects of SiO2–gentamicin nanohybrids on the behaviors of stem cells or other regular osteoblasts should be conducted to make a full evaluation of the safety of SiO2–gentamicin nanohybrids in orthopedic applications. PMID:29445277

  12. Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity

    PubMed Central

    Jaikumkao, Krit; Pongchaidecha, Anchalee; Thongnak, La-ongdao; Wanchai, Keerati; Arjinajarn, Phatchawan; Chatsudthipong, Varanuj; Chattipakorn, Nipon; Lungkaphin, Anusorn

    2016-01-01

    Gentamicin is a commonly used aminoglycoside antibiotic. However, its therapeutic use is limited by its nephrotoxicity. The mechanisms of gentamicin-induced nephrotoxicity are principally from renal inflammation and oxidative stress. Since atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exerts lipid-lowering effects, antioxidant, anti-inflammatory as well as anti-apoptotic effects, this study aimed to investigate the protective effects of atorvastatin against gentamicin-induced nephrotoxicity. Male Sprague Dawley rats were used and nephrotoxicity was induced by intraperitoneal injection of gentamicin, 100 mg/kg/day, for 15 days. Atorvastatin, 10 mg/kg/day, was administered by orally gavage 30 min before gentamicin injection on day 1 to 15 (pretreatment) or on day 10 to15 (delayed treatment). For only atorvastatin treatment group, it was given on day 1 to 15. At the end of the experiment, kidney weight, blood urea nitrogen and serum creatinine as well as renal inflammation (NF-κB, TNFαR1, IL-6 and iNOS), renal fibrosis (TGFβ1), ER stress (calpain, GRP78, CHOP, and caspase 12) and apoptotic markers (cleaved caspase-3, Bax, and Bcl-2) as well as TUNEL assay were determined. Gentamicin-induced nephrotoxicity was confirmed by marked elevations in serum urea and creatinine, kidney hypertrophy, renal inflammation, fibrosis, ER stress and apoptosis and attenuation of creatinine clearance. Atorvastatin pre and delayed treatment significantly improved renal function and decreased renal NF-κB, TNFαR1, IL-6, iNOS and TGFβ1 expressions. They also attenuated calpain, GRP78, CHOP, caspase 12, Bax, and increased Bcl-2 expressions in gentamicin-treated rat. These results indicate that atorvastatin treatment could attenuate gentamicin-induced nephrotoxicity in rats, substantiated by the reduction of inflammation, ER stress and apoptosis. The effect of atorvastatin in protecting from renal damage induced by gentamicin seems to be more effective when it beginning given along with gentamicin or pretreatment. PMID:27727327

  13. [Once-daily gentamicin dosing versus thrice-daily dosing in infants with acute pyelonephritis].

    PubMed

    Calvo Rey, C; García Díaz, B; Nebreda Pérez, V; García García, M L; Maderuelo Sánchez, A I; Cilleruelo Pascual, M L; García Lacalle, C

    2003-03-01

    Once-daily dosing (ODD) of gentamicin is advocated as an effective and safe treatment of Gram-negative bacterial infections in adults. There are insufficient data in the literature to justify its use in infants. To compare the efficacy of ODD of gentamicin with that of classical thrice-daily (t.i.d.) administration in infants with acute pyelonephritis. We performed a quasi-experimental study comparing 33 infants who received ODD of gentamicin with a historical control group of 25 infants treated with gentamicin t.i.d. Leukocytosis, C-reactive protein, creatinine, gentamicin dose, peak and trough values, time required for disappearance of fever, and outcome were analyzed. The mean doses of gentamicin (mg/kg/day) were higher in the t.i.d. group (6.4 1.14) than in the ODD group (5.06 0.22; p < 0.001). Peak serum gentamicin concentrations (micro g/ml) were significantly higher in the ODD group (9.32 1.4) than in the t.i.d. group (5.09 1.15; p < 0.001). Mean trough gentamicin concentrations (micro g/ml) were lower in the ODD group than in the t.i.d. group (0.23 0.26 vs 0.78 0.45; p 0.001). There were no significant differences in the duration of fever between the groups (30.64 32 hours in the t.i.d. group vs. 28.57 32 hours in the ODD group). Serum creatinine levels were normal during treatment in both groups. In all patients outcome was good and no adverse effects were noted. Treatment with ODD of gentamicin in our population of infants with acute pyelonephritis was as effective as traditional administration t.i.d. and possibly was equally safe or safer.

  14. Infection rates of rifampin/gentamicin-coated Titan Coloplast penile implants. Comparison with Inhibizone-impregnated AMS penile implants.

    PubMed

    Dhabuwala, Chirpriya; Sheth, Sheila; Zamzow, Brent

    2011-01-01

    It is a common practice to soak Titan(®) Coloplast penile implants in antibiotic solution prior to implantation. Experience with Inhibizone impregnation suggests that rifampin coating significantly reduces infection rates of penile implant surgery. In this article we describe the results of coating Titan Coloplast penile implants with rifampin/gentamicin solution. To compare infection rates of Titan(®) Coloplast penile implants coated with vancomycin/gentamycin, rifampin/gentamicin, and Inhibizone-impregnated American Medical Systems (AMS) penile implants. Chart review was done for all Mentor/Coloplast and AMS implant surgeries performed at our center between the dates January 1, 2002 and February 8, 2010. Infection rates for Titan(®) Coloplast penile implants coated with vancomycin/gentamycin, rifampin/gentamicin, and Inhibizone-impregnated (AMS) penile implants were compared. Infection rates for penile implants coated with different antibiotics. Infection rates for Titan(®) Coloplast penile implants coated with vancomycin/gentamycin and Inhibizone-impregnated (AMS) penile implants was 4.4% and 1.3%, respectively (P = 0.05). None of the rifampin/gentamicin-coated Titan(®) Coloplast penile implants have developed infection. Rifampin is the common antibiotic both in rifampin/gentamicin-coated Coloplast implants and Inhibizone(®) . The infection rate in this combined rifampin/gentamicin-coated Titan Coloplast implants and Inhibizone-coated AMS implants group was 0.63% (P = 0.03). Both rifampin/gentamicin-coated Titan(®) Coloplast penile implants and Inhibizone-impregnated (AMS) penile implants appear to have lower infection rates compared with vancomycin/gentamycin-coated Titan(®) Coloplast penile implants The present study does not suggest superiority of rifampin/gentamicin-coated Titan(®) Coloplast penile implants or Inhibizone-impregnated (AMS) penile implants but we strongly suggest that all Titan(®) Coloplast penile implants should be coated with rifampin/gentamicin solution. © 2010 International Society for Sexual Medicine.

  15. Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats.

    PubMed

    Hosaka, E M; Santos, O F P; Seguro, A C; Vattimo, M F F

    2004-07-01

    The frequent use of nonsteroidal anti-inflammatory drugs (NSAID) in combination with gentamicin poses the additional risk of nephrotoxic renal failure. Cyclooxygenase-1 (COX-1) is the main enzyme responsible for the synthesis of renal vasodilator prostaglandins, while COX-2 participates predominantly in the inflammatory process. Both are inhibited by non-selective NSAID such as indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer renal side effects than non-selective inhibitors. The objective of the present study was to determine whether the combined use of rofecoxib and gentamicin can prevent the increased renal injury caused by gentamicin and indomethacin. Male Wistar rats (250-300 g) were treated with gentamicin (100 mg/kg body weight, ip, N = 7), indomethacin (5 mg/kg, orally, N = 7), rofecoxib (1.4 mg/kg, orally, N = 7), gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively) or gentamicin + indomethacin (100 and 5 mg/kg, respectively, N = 8) for 5 days. Creatinine clearance and alpha-glutathione-S-transferase concentrations were used as markers of renal injury. Animals were anesthetized with ether and sacrificed for blood collection. The use of gentamicin plus indomethacin led to worsened renal function (0.199 +/- 0.019 ml/min), as opposed to the absence of a nephrotoxic effect of rofecoxib when gentamicin plus rofexicob was used (0.242 +/- 0.011 ml/min). These results indicate that COX-2-selective inhibitors can be used as an alternative treatment to conventional NSAID, especially in situations in which risk factors for nephrotoxicity are present.

  16. Concentration gradient along the scala tympani after local application of gentamicin to the round window membrane.

    PubMed

    Plontke, Stefan K; Mynatt, Robert; Gill, Ruth M; Borgmann, Stefan; Salt, Alec N

    2007-07-01

    The distribution of gentamicin along the fluid spaces of the cochlea after local applications has never previously been demonstrated. Computer simulations have predicted that significant basal-apical concentration gradients might be expected, and histologic studies indicate that hair cell damage is greater at the base than at the apex after local gentamicin application. In the present study, gradients of gentamicin along the cochlea were measured. A recently developed method of sampling perilymph from the cochlear apex of guinea pigs was used in which the samples represent fluid originating from different regions along the scala tympani. Gentamicin concentration was determined in sequential apical samples that were taken after up to 3 hours of local application to the round window niche. Substantial gradients of gentamicin along the length of the scala tympani were demonstrated and quantified, averaging more than 4,000 times greater concentration at the base compared with the apex at the time of sampling. Peak concentrations and gradients for gentamicin varied considerably between animals, likely resulting from variations in round window membrane permeability and rates of perilymph flow. The large gradients for gentamicin demonstrated here in guinea pigs account for how it is possible to suppress vestibular function in some patients with a local application of gentamicin without damaging auditory function. Variations in round window membrane permeability and in perilymph flow could account for why hearing losses are observed in some patients.

  17. Concentration gradient along scala tympani following the local application of gentamicin to the round window membrane

    PubMed Central

    Plontke, Stefan K.; Mynatt, Robert; Gill, Ruth M.; Borgmann, Stefan; Salt, Alec N.

    2008-01-01

    Objectives The distribution of gentamicin along the fluid spaces of the cochlea following local applications has never previously been demonstrated. Computer simulations have predicted that significant basal-apical concentration gradients might be expected and histological studies indicate that hair cell damage is greater at the base than at the apex following local gentamicin application. In the present study, gradients of gentamicin along the cochlea were measured. Methods A recently-developed method of sampling perilymph from the cochlear apex of guinea pigs was used, in which the samples represent fluid originating from different regions along scala tympani. Gentamicin concentration was determined in sequential apical samples which were taken following up to three hours of local application to the round window niche. Results Substantial gradients of gentamicin along the length of scala tympani were demonstrated and quantified, averaging more than 4000 times greater concentration at the base compared to the apex at the time of sampling. Peak concentrations and gradients for gentamicin varied considerably between animals, likely resulting from variations in round window membrane permeability and rates of perilymph flow. Conclusions The large gradients for gentamicin demonstrated here in guinea pigs account for how it is possible to suppress vestibular function in some patients with a local application of gentamicin without damaging auditory function. Variations in round window membrane permeability and in perilymph flow could account for why hearing losses are observed in some patients. PMID:17603318

  18. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

    PubMed

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

    2016-03-01

    The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

  19. Preliminary Study on the Antibacterial Activity of Essential Oils Alone and in Combination with Gentamicin Against Extended-Spectrum β-Lactamase-Producing and New Delhi Metallo-β-Lactamase-1-Producing Klebsiella pneumoniae Isolates.

    PubMed

    Kwiatkowski, Paweł; Pruss, Agata; Grygorcewicz, Bartłomiej; Wojciuk, Bartosz; Dołęgowska, Barbara; Giedrys-Kalemba, Stefania; Kochan, Ewa; Sienkiewicz, Monika

    2018-04-30

    The aim of the study was to investigate possible synergistic effects between several selected, commercially available essential oils and gentamicin against extended-spectrum β-lactamase (ESBL)-producing and New Delhi metallo-β-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae isolates. ESBLs production was confirmed by double-disk synergy test. Isolates positive for bla NDM-1 gene were found among the tested strains. K. pneumoniae ATCC ® BAA-1705™ strain was used as a control. The checkerboard method was applied to assess the synergistic and additive action of nine essential oils: caraway, fennel, peppermint, geranium, basil, clove, thyme, clary sage, and lavender, respectively, in combination with gentamicin. Our results indicated that peppermint oil combined with gentamicin showed synergistic activity against both control, ESBL-producing and NDM-1-producing isolates. Caraway essential oil demonstrated synergy with gentamicin toward ESBL-producing and additionally gentamicin-resistant strains. The additive effect was observed for gentamicin combined with thyme, fennel, basil, and clary sage. Because of their synergistic activity with gentamicin, peppermint, and caraway oils in particular, can be considered as an alternative or an addition for the control of infections with limited therapeutic options due to multidrug resistance.

  20. 21 CFR 524.1044b - Gentamicin and betamethasone otic solution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... treatment of acute and chronic otitis externa caused by bacteria sensitive to gentamicin in dogs, instill... of infected superficial lesions caused by bacteria sensitive to gentamicin in dogs and cats, apply a...

  1. Citrullus colocynthis failed to combat against renal derangements, in spite of its strong antioxidant properties.

    PubMed

    Ullah, Naveed; Khan, Mir Azam; Asif, Afzal Haq; Khan, Taous; Ahmad, Waqar

    2013-01-01

    Gentamicin is a potent antibiotic, effective against Gram negative bacteria. The most common adverse effect of gentamicin is nephrotoxicity. Present study was aimed to explore the protective potentials of Citrullus colocynthis against gentamicin induced nephrotoxicity due to its strong antioxidant properties. Toxic doses of gentamicin (80 mg/kg/day, i.m.) were administered alone and as co-therapy with the extract of C. colocynthis (25 mg/kg/day, p.o.). Physiological, biochemical and histological examinations were performed to compare the experimental and toxic groups (n = 6) with control group animals. Co-therapy of C. colocynthis with gentamicin protected changes in the body weight, blood urea nitrogen, creatinine clearance, proteins and lactate dehydrogenase excretions. However, a significant rise in serum creatinine and serum uric acid with fall in serum calcium and serum potassium was observed, which were significantly different from control group animals. Necrotic and ruptured tubules were also found abundantly. This study revealed that co-theapy of C. colocynthis with gentamicin for twenty one days, failed to protect renal injury associated by gentamicin in spite of its strong antioxidant properties.

  2. In vitro susceptibility testing of Malassezia pachydermatis to gentamicin.

    PubMed

    Silva, Freddy A; Ferrer, Otilia; Déniz, Soraya; Rosario, Inmaculada; Conde-Felipe, Magnolia; Díaz, Esther L; Acosta-Hernández, Begoña

    2017-08-01

    Two studies have observed that growth media containing gentamicin can inhibit the growth of the yeast organism Malassezia pachydermatis. The minimum inhibitory concentration (MIC) of this bactericidal antibiotic for this organism has not been previously determined. To evaluate the susceptibility of M. pachydermatis isolates to gentamicin. The MIC of gentamicin was determined using a modified version of the M27-A3 microdilution method following the guidelines of the Clinical and Laboratory Standards Institute. A modified Christensen's urea broth was used to enhance the growth of the M. pachydermatis isolates. Visual and spectrophotometric end-point readings were performed to detect the presence or absence of yeast growth. The MIC50 and MIC90 of gentamicin were 8.12 μg/mL and 32.5 μg/mL, respectively; M. pachydermatis strains were classified as susceptible (S), intermediate (I) and resistant (R). The susceptibility of these isolates to gentamicin in vitro, by visual and spectrophotometric end-point reading, was: S, 54-56%; I, 40-41%; and R, 3-6%. Prospective MICs for M. pachydermatis have been established for gentamicin. © 2017 ESVD and ACVD.

  3. Salicylic Acid Attenuates Gentamicin-Induced Nephrotoxicity in Rats

    PubMed Central

    Randjelovic, Pavle; Veljkovic, Slavimir; Stojiljkovic, Nenad; Jankovic-Velickovic, Ljubinka; Sokolovic, Dusan; Stoiljkovic, Milan; Ilic, Ivan

    2012-01-01

    Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats. PMID:22666115

  4. Gentamicin pharmacokinetics in the chicken inner ear.

    PubMed

    Bunting, Eric C; Park, Debra L; Durham, Dianne; Girod, Douglas A

    2004-06-01

    Avians have the unique ability to regenerate cochlear hair cells that are lost due to ototoxins or excessive noise. Many methodological techniques are available to damage the hair cells for subsequent scientific study. A recent method utilizes topical application of an ototoxic drug to the round window membrane. The current study examines the pharmacokinetics of gentamicin in the inner ear of chickens following topical application to the round window membrane or a single systemic high dose given intraperitoneally. Chickens were given gentamicin topically or systemically and survived for 1, 4, 12, 24, or 120 h (controls at 4 and 120 h). Serum and perilymph samples were obtained prior to sacrifice and measured for gentamicin levels. Results revealed higher levels of gentamicin in the perilymph of topically treated chickens than systemically treated chickens, with significant amounts of gentamicin still present in both at the latest survival time of 5 days. As expected, systemically treated chickens had much higher levels of gentamicin in the serum than topically treated chickens. Advantages and disadvantages to each method of drug administration are discussed.

  5. Monte Carlo Simulation of Nanoparticle Encapsulation in Flames

    NASA Technical Reports Server (NTRS)

    Sun, Z.; Huertas, J. I.; Axelbaum, R. L.

    1999-01-01

    Two critical challenges facing the application of flames for synthesis of nanopowder materials are: (1) overcoming formation of agglomerates and (2) ensuring that the highly reactive nanopowders that are synthesized in flames can be produced in such a manner that their purity is maintained during subsequent processing. Agglomerates are produced in flames because particle formation occurs in a high temperature and high number density environment. They are undesirable in most advanced applications of powders. For example, agglomerates have a deleterious effect on compaction density, leading to voids when nanopowders are consolidated. Efforts to avoid agglomeration in flames without substantially reducing particle number density and, consequently, production rate, have had limited success. Powder purity must also be maintained during subsequent handling of nanopowders and this poses a significant challenge for any synthesis route because nanopowders, particularly metals and non-oxide ceramic powders, are inherently reactive. Impurities acquired during handling of nanopowders have slowed the advancement of the nanostructured materials industry. One promising approach that has been proposed to address these problems is nano-encapsulation. In this approach, the core particles are encapsulated in a removable material while they are within the flame but before excessive agglomeration has occurred. Condensation can be very rapid so that core particles are trapped within the condensed material and agglomeration is limited. Nano-encapsulation also addresses the handling concerns for post-synthesis processing. Results have shown that when nano-encapsulated powders are exposed to atmosphere the core particles are protected from oxidation and/or hydrolysis. Thus, handling of the powders does not require extreme care. If, for example, at the time of consolidation the encapsulation material is removed by vacuum annealing, the resulting powder remains unagglomerated and free of impurities. In this work, we described a novel aerosol model that has been developed to simulate particle encapsulation in flames. The model will ultimately be coupled to a one-dimensional spherical flame code and compared to results from microgravity flame experiments.

  6. Preparation and Properties of Hybrid Nanostructures of Zinc Tetraphenylporphyrinate and an Amphiphilic Copolymer of N-Vinylpyrrolidone in a Neutral Aqueous Buffer Solution

    NASA Astrophysics Data System (ADS)

    Kurmaz, S. V.; Gak, V. Yu.; Kurmaz, V. A.; Konev, D. V.

    2018-02-01

    Water-soluble forms of a hydrophobic dye, zinc tetraphenylporphyrinate, are obtained via its solubilization by polymer particles of the micellar type formed by a copolymer of N-vinylpyrrolidone with triethylene glycol dimethacrylate. Hydrodynamic radii R h and the size distribution of such particles in neutral aqueous buffer solutions are determined via dynamic light scattering. The electrochemical activity of the encapsulated dye is found, and its photochemical properties (absorption and fluorescence) are studied.

  7. Development and characterization of polymer-oil nanostructured carrier (PONC) for controlled delivery of all-trans retinoic acid (ATRA)

    NASA Astrophysics Data System (ADS)

    Narvekar, Mayuri M.

    The commonly used PLGA-based delivery systems are often limited by their inadequate drug loading and release properties. This study reports the integration of oil into PLGA to form the prototype of a hybrid drug carrier PONC. Our primary goal is to confer the key strength of lipid-based drug carriers, i.e. efficient encapsulation of lipophilic compounds, to a PLGA system without taking away its various useful qualities. The PONC were formulated by emulsification solvent evaporation technique, which were then characterized for particle size, encapsulation efficiency, drug release and anticancer efficacy. The ATRA loaded PONC showed excellent encapsulation efficiency and release kinetics. Even after surface functionalization with PEG , controlled drug release kinetics was maintained, with 88.5% of the encapsulated ATRA released from the PEG-PONC in a uniform manner over 120 hours. It also showed favorable physicochemical properties and serum stability. PEG-PONC has demonstrated substantially superior activity over the free ATRA in ovarian cancer cells that are non-responsive to the standard chemotherapy. The newly developed PEG-PONC significantly reduced the IC50 values (p<0.05) in the chemoresistant cells in both MTT and colony formation assays. Hence, this new ATRA-nanoformulation may offer promising means for the delivery of lipophilic compounds like all-trans retinoic acid to treat highly resistant ovarian cancer.

  8. Free-Standing Hybrid Graphene Paper Encapsulating Nanostructures for High Cycle-Life Supercapacitors.

    PubMed

    Jiao, Xinyan; Hao, Qingli; Xia, Xifeng; Lei, Wu; Ouyang, Yu; Ye, Haitao; Mandler, Daniel

    2018-03-09

    The incorporation of spacers between graphene sheets has been investigated as an effective method to improve the electrochemical performance of graphene papers (GPs) for supercapacitors. Here, we report the design of free-standing GP@NiO and GP@Ni hybrid GPs in which NiO nanoclusters and Ni nanoparticles are encapsulated into graphene sheets through electrostatic assembly and subsequent vacuum filtration. The encapsulated NiO nanoclusters and Ni nanoparticles can mitigate the restacking of graphene sheets, providing sufficient spaces for high-speed ion diffusion and electron transport. In addition, the spacers strongly bind to graphene sheets, which can efficiently improve the electrochemical stability. Therefore, at a current density of 0.5 A g -1 , the GP@NiO and GP@Ni electrodes exhibit higher specific capacitances of 306.9 and 246.1 F g -1 than the GP electrode (185.7 F g -1 ). The GP@NiO and GP@Ni electrodes exhibit capacitance retention of 98.7 % and 95.6 % after 10000 cycles, demonstrating an outstanding cycling stability. Additionally, the GP@NiO∥GP@Ni delivers excellent cycling stability (93.7 % after 10 000 cycles) and high energy density. These free-standing encapsulated hybrid GPs have great potential as electrode for high-performance supercapacitors. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. [Individualized monitoring of the therapy with gentamycin using pharmacokinetic methods. Which method to choose?].

    PubMed

    Carvalho, A; Fonseca, C; Falcão, F; Pereira, T A; Freitas, O; Parrinha, A; Costa, M; Rodrigues, M J; Ceia, F; Luís, A S

    1996-01-01

    Gentamicin has an excellent cost/efficacy ratio for gram negative infections treatment. Its use is often limited in clinical practice by its narrow safety margins and a high incidence of toxicity. Gentamicin related nephrotoxicity is a major adverse effect, mostly in patients with other concomitant potential risk factors. As many other Authors we have found in our Internal Medicine Service during 1992 a gentamicin related nephrotoxicity incidence of 22.5%. Various empiric methods and nomograms have shown a significant incidence of error in predicting individualized gentamicin dosage regimens. Pharmacokinetics methods have demonstrated much better results regarding efficacy and toxicity. The aim of this prospective study carried out during 1993-1994 was to individualize by pharmacokinetics methods dosage regimens of gentamicin in patients with one or more concomitant risk factors of nephrotoxicity. The purpose of pharmacokinetics dosage regimens has been to achieve trough serum concentrations of gentamicin in therapeutics range-0.5 to 2 micrograms/ml-on the first 24 to 48 hours of treatment, and the maintenance in this range during all the treatment, avoiding both toxic and under therapeutic levels. The incidence of gentamicin related nephrotoxicity has been evaluated in this population. Twenty patients were studied: 18 males and 2 females aged 59.6 years (19 to 85). All had one or more potential risk factors for nephrotoxicity-65 years or more: 13, previous renal failure: 6, other nephrotoxic drugs: 10, diuretics: 4, dehydration: 5, congestive heart failure: 5, diabetes: 3, hypertension: 3. For the first 10 patients gentamicin dosage regimens have been determined by Sawchuk-Zaske pharmacokinetics method and for the subsequent 10 patients by Bayesian method. The two subpopulations had no significant differences regarding mean age, sex and potential risk factors for nephrotoxicity. Results of Sawchuk-Zaske method: 53 trough gentamicin serum concentration were obtained; 86.8% were within the therapeutic range, 7.5% were toxic and 5.7% were under therapeutic. Results of Bayesian method: 44 determinations of gentamicin through concentrations were obtained; 86.3% within therapeutic range, 2.4% were toxic and 11.3% were under therapeutic. A great variability in pharmacokinetic patient's profile has been found and explains the great variability of individualized dosage regimens of gentamicin (30 to 320 mg/day). No patients had gentamicin related nephrotoxicity. Both pharmacokinetics methods lead to a efficient and save employment of gentamicin in patients with previous renal failure and other potential risk factors for nephrotoxicity.

  10. The use of intravesical gentamicin to treat recurrent urinary tract infections in lower urinary tract dysfunction.

    PubMed

    Abrams, Paul; Hashim, Hashim; Tomson, Charles; Macgowan, Alasdair; Skews, Rachel; Warren, Katherine

    2017-11-01

    To assess the use of intravesical gentamicin to treat intractable recurrent urinary tract infections in lower urinary tract dysfunction. A two-center retrospective cohort study of 27 patients treated with intravesical gentamicin was performed over a 2-year period. A treatment protocol was developed, reviewed, and accepted by the clinical effectiveness committee of both hospitals. Patients were taught to instill the gentamicin into the bladder on a nightly basis. Inclusion criteria included failure to respond to standard therapy, having six or more cultured confirmed UTIs over a 12-month period, or at least one hospital admission with sepsis. Serum gentamicin levels were taken after 7 days and the treatment was discontinued if the level was >1 mg/L. Patients were counseled about the limited evidence base for this treatment. Twenty-seven patients have been treated with intravesical gentamicin for an average of 26 months. Seventeen were performing ISC, five had suprapubic catheters, three were voiding, and two had ileal conduits at the time of instituting treatment. All patients started on daily 80 mg gentamicin. Twenty two patients had less frequently occurring infections after starting intravesical gentamicin treatment. Six stopped the treatment and none had side effects as a result of the instillations. This study has shown that in a small group of adult patients who have multiple symptomatic UTIs refractory to conventional treatment, intravesical gentamicin is effective in reducing the frequency of infections. The treatment is well tolerated with no evidence of systemic absorption. © 2017 Wiley Periodicals, Inc.

  11. Burkholderia pseudomallei Isolates from Sarawak, Malaysian Borneo, Are Predominantly Susceptible to Aminoglycosides and Macrolides

    PubMed Central

    Podin, Yuwana; Sarovich, Derek S.; Price, Erin P.; Kaestli, Mirjam; Mayo, Mark; Hii, KingChing; Ngian, HieUng; Wong, SeeChang; Wong, IngTien; Wong, JinShyan; Mohan, Anand; Ooi, MongHow; Fam, TemLom; Wong, Jack; Tuanyok, Apichai; Keim, Paul; Giffard, Philip M.

    2014-01-01

    Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei. Resistance to gentamicin is generally a hallmark of B. pseudomallei, and gentamicin is a selective agent in media used for diagnosis of melioidosis. In this study, we determined the prevalence and mechanism of gentamicin susceptibility found in B. pseudomallei isolates from Sarawak, Malaysian Borneo. We performed multilocus sequence typing and antibiotic susceptibility testing on 44 B. pseudomallei clinical isolates from melioidosis patients in Sarawak district hospitals. Whole-genome sequencing was used to identify the mechanism of gentamicin susceptibility. A novel allelic-specific PCR was designed to differentiate gentamicin-sensitive isolates from wild-type B. pseudomallei. A reversion assay was performed to confirm the involvement of this mechanism in gentamicin susceptibility. A substantial proportion (86%) of B. pseudomallei clinical isolates in Sarawak, Malaysian Borneo, were found to be susceptible to the aminoglycoside gentamicin, a rare occurrence in other regions where B. pseudomallei is endemic. Gentamicin sensitivity was restricted to genetically related strains belonging to sequence type 881 or its single-locus variant, sequence type 997. Whole-genome sequencing identified a novel nonsynonymous mutation within amrB, encoding an essential component of the AmrAB-OprA multidrug efflux pump. We confirmed the role of this mutation in conferring aminoglycoside and macrolide sensitivity by reversion of this mutation to the wild-type sequence. Our study demonstrates that alternative B. pseudomallei selective media without gentamicin are needed for accurate melioidosis laboratory diagnosis in Sarawak. This finding may also have implications for environmental sampling of other locations to test for B. pseudomallei endemicity. PMID:24145517

  12. Burkholderia pseudomallei isolates from Sarawak, Malaysian Borneo, are predominantly susceptible to aminoglycosides and macrolides.

    PubMed

    Podin, Yuwana; Sarovich, Derek S; Price, Erin P; Kaestli, Mirjam; Mayo, Mark; Hii, KingChing; Ngian, Hieung; Wong, SeeChang; Wong, IngTien; Wong, JinShyan; Mohan, Anand; Ooi, MongHow; Fam, TemLom; Wong, Jack; Tuanyok, Apichai; Keim, Paul; Giffard, Philip M; Currie, Bart J

    2014-01-01

    Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei. Resistance to gentamicin is generally a hallmark of B. pseudomallei, and gentamicin is a selective agent in media used for diagnosis of melioidosis. In this study, we determined the prevalence and mechanism of gentamicin susceptibility found in B. pseudomallei isolates from Sarawak, Malaysian Borneo. We performed multilocus sequence typing and antibiotic susceptibility testing on 44 B. pseudomallei clinical isolates from melioidosis patients in Sarawak district hospitals. Whole-genome sequencing was used to identify the mechanism of gentamicin susceptibility. A novel allelic-specific PCR was designed to differentiate gentamicin-sensitive isolates from wild-type B. pseudomallei. A reversion assay was performed to confirm the involvement of this mechanism in gentamicin susceptibility. A substantial proportion (86%) of B. pseudomallei clinical isolates in Sarawak, Malaysian Borneo, were found to be susceptible to the aminoglycoside gentamicin, a rare occurrence in other regions where B. pseudomallei is endemic. Gentamicin sensitivity was restricted to genetically related strains belonging to sequence type 881 or its single-locus variant, sequence type 997. Whole-genome sequencing identified a novel nonsynonymous mutation within amrB, encoding an essential component of the AmrAB-OprA multidrug efflux pump. We confirmed the role of this mutation in conferring aminoglycoside and macrolide sensitivity by reversion of this mutation to the wild-type sequence. Our study demonstrates that alternative B. pseudomallei selective media without gentamicin are needed for accurate melioidosis laboratory diagnosis in Sarawak. This finding may also have implications for environmental sampling of other locations to test for B. pseudomallei endemicity.

  13. High sensitive virus and bacteria detection using plasma-surface-functionalized and antibody-integrated carbon nanomaterials

    NASA Astrophysics Data System (ADS)

    Nagatsu, Masaaki

    2015-09-01

    In this study we will present our recent results on the virus and bacteria detection system using the surface-functionalized carbon-encapsulated magnetic nanoparticles (NPs) fabricated by dc arc discharge, and carbon nanotube(CNT) dot-array prepared with a combined thermal and plasma CVD system. Surface functionalization of their surfaces has been carried out by plasma chemical modification using a low-pressure RF plasma for carbon-encapsulated magnetic NPs, and an ultrafine atmospheric pressure plasma jet(APPJ) for CNT dot-array substrate. After immobilization of the relevant biomolecules onto the surface of nano-structured materials, we have carried out the experiments on virus or bacteria detection using these surface-functionalized nano-structured materials. From the preliminary experiments with carbon-encapsulated magnetic NPs, we confirmed that influenza A (H1N1) virus concentration of 17.3-fold was achieved by using anti-influenza A virus hemagglutinin (HA) antibody. We have also confirmed a rapid and sensitive detection of Salmonella using the proposed method. The feasibility of CNT dot-array as a microarray biosensor has been studied by maskless functionalization of amino (-NH2) and carboxyl (-COOH) groups onto CNTs by using a ultrafine APPJ with a micro-capillary. The experimental results of chemical derivatization with the fluorescent dye showed that the CNT dot-array was not only functionalized with amino group and carboxyl group, but was also functionalized without any interference between functional groups. The success of maskless functionalization in the line pattern provides a feasibility of a multi-functionalization CNT dot-array device for future application of a microarray biosensor. This work has been supported in part by Grant-in-Aid for Scientific Research (Nos. 21110010 and 25246029) from the JSPS and the International Research Collaboration and Scientific Publication Grant (DIPA-23.04.1.673453/2015) from DGHE Indonesia.

  14. In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile

    PubMed Central

    Stallmann, Hein P; Faber, Chris; Bronckers, Antonius LJJ; Nieuw Amerongen, Arie V; Wuisman, Paul IJM

    2006-01-01

    Background Polymethyl-methacrylate (PMMA) beads releasing antibiotics are used extensively to treat osteomyelitis, but require surgical removal afterwards because they do not degrade. Methods As an alternative option, this report compares the in vitro gentamicin release profile from clinically used, biodegradable carrier-materials: six injectable cements and six granule-types. Cement cylinders and coated granules containing 3% gentamicin were submerged in dH2O and placed in a 48-sample parallel drug-release system. At regular intervals (30, 90, 180 min. and then every 24 h, for 21 days), the release fluid was exchanged and the gentamicin concentration was measured. The activity of released gentamicin was tested on Staphylococcus aureus. Results All combinations showed initial burst-release of active gentamicin, two cements had continuous-release (17 days). The relative release of all cements (36–85%) and granules (30–62%) was higher than previously reported for injectable PMMA-cements (up to 17%) and comparable to other biodegradable carriers. From the cements residual gentamicin could be extracted, whereas the granules released all gentamicin that had adhered to the surface. Conclusion The high release achieved shows great promise for clinical application of these biodegradable drug-carriers. Using the appropriate combination, the required release profile (burst or sustained) may be achieved. PMID:16504140

  15. THE EFFECT OF FICUS CARICA L. (ANJIR) LEAF EXTRACT ON GENTAMICIN INDUCED NEPHROTOXICITY IN ADULT MALE ALBINO MICE.

    PubMed

    Ghaffar, Ammara; Tahir, Mohammad; Lone, Khalid Pervez; Faisal, Bushra; Latif, Waqas

    2015-01-01

    Gentamicin is an aminoglycoside isolated from Micromonospora purpurea known for its nephrotoxicity. Ficus carica L is known to treat many ailments. This study was designed to investigate the effects of Ficus carica L. (Anjir) leaf extract on renal oxidative stress induced by gentamicin in albino mice. In this laboratory based experimental study 30 mice were divided into three groups, containing 10 mice each. Group A being the control; groups B and C were experimental and treated with gentamicin 200 mg/kg/day intraperitoneally and, Ficus carica L. leaf extract 400 mg/kg/day orally with gentamicin 200 mg/kg/day intraperitoneally respectively for a period of 8 days. Blood samples were taken 24 hours after completion of the experimental period by cardiac puncture under anesthesia and kidneys of each mouse were taken out for microscopic examination. Gentamicin treatment increased serum urea and creatinine levels (group B). Ficus carica L. leaf extract treated animals showed significant reduction in biochemical markers of kidney functions in group C. The histopathological examination of group A showed normal renal structure which was deranged in group B treated with only gentamicin, whereas, group C exhibited marked improvement in histological structure. Ficus carica L. leaf extract is effective in preventing gentamicin induced functional and structural changes in kidney of albino mice.

  16. Hydrogel iontophoresis for gentamicin administration to the rabbit eye

    NASA Astrophysics Data System (ADS)

    Eljarrat-Binstock, Esther; Raiskup, Frederik; Frucht-Pery, Joseph; Domb, Abraham J.

    2005-04-01

    Iontophoresis (IONT) is a non-invasive technique in which a low electric current is used to enhance the penetration of charged molecules into tissue. This technique has been used in various fields of medicine, mostly in transdermal drug delivery. This study was aimed to evaluate the efficacy and the distribution profile of gentamicin using corneal IONT on infected and healthy rabbit eyes. Corneal iontophoresis of gentamicin sulfate was studied using drug-loaded disposable hydrogel probes mounted on a portable iontophoretic device, applying a low current for 60 seconds. This study confirmed that a triple iontophoretic treatment of gentamicin for only 60 seconds (0.5mA) significantly reduces the count of pseudomonas in the infected cornea to a non-infectious level. Peak gentamicin concentrations at the healthy corneas (363.1 +/- 127.3 μg/g) and at the aqueous humor (29.4 +/- 17.4 μg/ml) were reached immediately and two hours after a single iontophoretic treatment, respectively. The concentration versus time profile of gentamicin following iontophoresis revealed a gentamicin half life of 2.07 h in the anterior chamber, and a clearance of 1.73 μl/min from the anterior chamber to the posterior segments of the eye. This study indicates that a short iontophoretic treatment using gentamicin-loaded hydrogels has a potential clinical value in treating corneal infections, by increasing drug penetration to the eye and maintaining therapeutic levels for more than eight hours.

  17. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mumin, Md Abdul, E-mail: pcharpentier@eng.uwo.ca; Akhter, Kazi Farida, E-mail: pcharpentier@eng.uwo.ca; Charpentier, Paul A., E-mail: pcharpentier@eng.uwo.ca

    Semiconductor nanocrystals (NCs) (also known as quantum dots, QDs) have attracted immense attention for their size-tunable optical properties that makes them impressive candidates for solar cells, light emitting devices, lasers, as well as biomedical imaging. However monodispersity, high and consistent photoluminescence, photostability, and biocompatibility are still major challenges. This work focuses on optimizing the photophysical properties and biocompatibility of QDs by forming core-shell nanostructures and their encapsulation by a carrier. Highly luminescent CdS and CdS-ZnS core-shell QDs with 5 nm sizes were synthesized using a facile approach based on pyrolysis of the single molecule precursors. After capping the CdS QDsmore » with a thin layer of ZnS to reduce toxicity, the photoluminescence and photostability of the core-shell QDs was significantly enhanced. To make both the bare and core/shell structure QDs more resistant against photochemical reactions, a mesoporous silica layer was grown on the QDs through a reverse microemulsion technique based on hydrophobic interaction. This encapsulation enhanced the quantum yield and photostability compared to the bare QDs by providing much stronger resistance to oxidation and Oswald ripening of QDs. Encapsulation also improved biocompatibility of QDs that was evaluated with human umbilical vein endothelial cell lines (HUVEC)« less

  18. Encapsulation of Fe3O4 Nanoparticles into N, S co-Doped Graphene Sheets with Greatly Enhanced Electrochemical Performance

    PubMed Central

    Yang, Zunxian; Qian, Kun; Lv, Jun; Yan, Wenhuan; Liu, Jiahui; Ai, Jingwei; Zhang, Yuxiang; Guo, Tailiang; Zhou, Xiongtu; Xu, Sheng; Guo, Zaiping

    2016-01-01

    Particular N, S co-doped graphene/Fe3O4 hybrids have been successfully synthesized by the combination of a simple hydrothermal process and a subsequent carbonization heat treatment. The nanostructures exhibit a unique composite architecture, with uniformly dispersed Fe3O4 nanoparticles and N, S co-doped graphene encapsulant. The particular porous characteristics with many meso/micro holes/pores, the highly conductive N, S co-doped graphene, as well as the encapsulating N, S co-doped graphene with the high-level nitrogen and sulfur doping, lead to excellent electrochemical performance of the electrode. The N-S-G/Fe3O4 composite electrode exhibits a high initial reversible capacity of 1362.2 mAhg−1, a high reversible specific capacity of 1055.20 mAhg−1 after 100 cycles, and excellent cycling stability and rate capability, with specific capacity of 556.69 mAhg−1 when cycled at the current density of 1000 mAg−1, indicating that the N-S-G/Fe3O4 composite is a promising anode candidate for Li-ion batteries. PMID:27296103

  19. Effect of Catechins, Green tea Extract and Methylxanthines in Combination with Gentamicin Against Staphylococcus aureus and Pseudomonas aeruginosa

    PubMed Central

    Fazly Bazzaz, Bibi Sedigheh; Sarabandi, Sahar; Khameneh, Bahman; Hosseinzadeh, Hossein

    2016-01-01

    Objectives: Bacterial resistant infections have become a global health challenge and threaten the society’s health. Thus, an urgent need exists to find ways to combat resistant pathogens. One promising approach to overcoming bacterial resistance is the use of herbal products. Green tea catechins, the major green tea polyphenols, show antimicrobial activity against resistant pathogens. The present study aimed to investigate the effect of catechins, green tea extract, and methylxanthines in combination with gentamicin against standard and clinical isolates of Staphylococcus aureus (S. aureus) and the standard strain of Pseudomonas aeruginosa (P. aeruginosa). Methods: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) values of different agents against bacterial strains were determined. The interactions of green tea extract, epigallate catechin, epigallocatechin gallate, two types of methylxanthine, caffeine, and theophylline with gentamicin were studied in vitro by using a checkerboard method and calculating the fraction inhibitory concentration index (FICI). Results: The MICs of gentamicin against bacterial strains were in the range of 0.312 - 320 μg/mL. The MIC values of both types of catechins were 62.5 - 250 μg/ mL. Green tea extract showed insufficient antibacterial activity when used alone. Methylxanthines had no intrinsic inhibitory activity against any of the bacterial strains tested. When green tea extract and catechins were combined with gentamicin, the MIC values of gentamicin against the standard strains and a clinical isolate were reduced, and synergistic activities were observed (FICI < 1). A combination of caffeine with gentamicin did not alter the MIC values of gentamicin. Conclusion: The results of the present study revealed that green tea extract and catechins potentiated the antimicrobial action of gentamicin against some clinical isolates of S. aureus and standard P. aeruginosa strains. Therefore, combinations of gentamicin with these natural compounds might be a promising approach to combat microbial resistance. PMID:28097041

  20. Protective Effect of Bauhinia purpurea on Gentamicin-induced Nephrotoxicity in Rats

    PubMed Central

    Lakshmi, B. V. S.; Neelima, N.; Kasthuri, N.; Umarani, V.; Sudhakar, M.

    2009-01-01

    The present study was undertaken to evaluate the ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea for its protective effects on gentamicin-induced nephrotoxicity in rats. Nephrotoxicity was induced in Wistar rats by intraperitoneal administration of gentamicin 100 mg/kg/d for eight days. Effect of concurrent administration of ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea at a dose of 300 mg/kg/d given by oral route was determined using serum creatinine, serum uric acid, blood urea nitrogen and serum urea as indicators of kidney damage. The study groups contained six rats in each group. It was observed that the ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea significantly protect rat kidneys from gentamicin-induced histopathological changes. Gentamicin-induced glomerular congestion, blood vessel congestion, epithelial desquamation, accumulation of inflammatory cells and necrosis of the kidney cells were found to be reduced in the groups receiving the leaf and unripe pods extract of Bauhinia purpurea along with gentamicin. The extracts also normalized the gentamicin-induced increase in serum creatinine, serum uric acid and blood urea nitrogen levels. This is also evidenced by the histopathological studies. PMID:20502576

  1. Activity of Daptomycin Alone and in Combination with Rifampin and Gentamicin against Staphylococcus aureus Assessed by Time-Kill Methodology▿ †

    PubMed Central

    Credito, Kim; Lin, Gengrong; Appelbaum, Peter C.

    2007-01-01

    The synergistic effects of daptomycin plus gentamicin or rifampin were tested against 50 Staphylococcus aureus strains, with daptomycin MICs ranging between 0.25 and 8 μg/ml. Daptomycin sub-MICs combined with gentamicin concentrations lower than the MIC yielded synergy in 34 (68%) of the 50 strains. Daptomycin combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus strain only, and virtually all synergy occurred between daptomycin and gentamicin. PMID:17220402

  2. Activity of daptomycin alone and in combination with rifampin and gentamicin against Staphylococcus aureus assessed by time-kill methodology.

    PubMed

    Credito, Kim; Lin, Gengrong; Appelbaum, Peter C

    2007-04-01

    The synergistic effects of daptomycin plus gentamicin or rifampin were tested against 50 Staphylococcus aureus strains, with daptomycin MICs ranging between 0.25 and 8 microg/ml. Daptomycin sub-MICs combined with gentamicin concentrations lower than the MIC yielded synergy in 34 (68%) of the 50 strains. Daptomycin combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus strain only, and virtually all synergy occurred between daptomycin and gentamicin.

  3. Voriconazole-Loaded Nanostructured Lipid Carriers for Ocular Drug Delivery.

    PubMed

    Andrade, Lígia M; Rocha, Kamilla A D; De Sá, Fernando A P; Marreto, Ricardo N; Lima, Eliana M; Gratieri, Tais; Taveira, Stephânia F

    2016-06-01

    To design and evaluate the potential of a topical delivery system for ocular administration of voriconazole, based on cationic nanostructured lipid carriers (NLCs). NLC dispersions composed of glyceryl behenate/capric caprylic triglyceride, polysorbate 80, sorbitan trioleate, and cetylpyridinium chloride were obtained and characterized. Ex vivo permeations experiments were performed to evaluate their drug delivery potential. NLCs presented a mean diameter of 250.2 ± 03.1 nm, narrow polydispersity index (0.288 ± 0.03), positive zeta potential (31.22 ± 3.8 mV), and over 75% encapsulation efficiency. Ex vivo ocular experiments proved that NLCs were able to deliver therapeutically relevant drug amounts to the cornea after only 30 minutes (13.88 ± 0.24 μg/cm). The formulation was nonexpensive, easy to prepare, and composed of well-tolerated and accepted excipients. Further in vivo experiments are necessary to confirm the improved performance and tolerability of the formulation.

  4. Preparation and characterization of carnauba wax nanostructured lipid carriers containing benzophenone-3.

    PubMed

    Lacerda, S P; Cerize, N N P; Ré, M I

    2011-08-01

    Nanostructured lipid carriers (NLCs) are potential active delivery systems based on mixtures of solid lipids and liquid oil. In this paper, aqueous dispersions of NLCs were prepared by a hot high-pressure homogenization technique using carnauba wax as the solid lipid and isodecyl oleate as the liquid oil. The preparation and stability parameters of benzophenone-3-loaded NLCs have been investigated concerning particle size, zeta potential and loading capacity to encapsulate benzophenone-3, a molecular sunscreen. The current investigation illustrates the effect of the composition of the lipid mixture on the entrapment efficiency, in vitro release and stability of benzophenone-3-loaded in these NLCs. A loading capacity of approximately 5% of benzophenone-3 (m(BZ-3) /m(lipids) ) was characteristic of these systems. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  5. Thermal protection of β-carotene in re-assembled casein micelles during different processing technologies applied in food industry.

    PubMed

    Sáiz-Abajo, María-José; González-Ferrero, Carolina; Moreno-Ruiz, Ana; Romo-Hualde, Ana; González-Navarro, Carlos J

    2013-06-01

    β-Carotene is a carotenoid usually applied in the food industry as a precursor of vitamin A or as a colourant. β-Carotene is a labile compound easily degraded by light, heat and oxygen. Casein micelles were used as nanostructures to encapsulate, stabilise and protect β-carotene from degradation during processing in the food industry. Self-assembly method was applied to re-assemble nanomicelles containing β-carotene. The protective effect of the nanostructures against degradation during the most common industrial treatments (sterilisation, pasteurisation, high hydrostatic pressure and baking) was proven. Casein micelles protected β-carotene from degradation during heat stabilisation, high pressure processing and the processes most commonly used in the food industry including baking. This opens new possibilities for introducing thermolabile ingredients in bakery products. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Scalable Super-Resolution Synthesis of Core-Vest Composites Assisted by Surface Plasmons.

    PubMed

    Montazeri, A O; Kim, Y; Fang, Y S; Soheilinia, N; Zaghi, G; Clark, J K; Maboudian, R; Kherani, N P; Carraro, C

    2018-02-15

    The behavior of composite nanostructures depends on both size and elemental composition. Accordingly, concurrent control of size, shape, and composition of nanoparticles is key to tuning their functionality. In typical core-shell nanoparticles, the high degree of symmetry during shell formation results in fully encapsulated cores with severed access to the surroundings. We commingle light parameters (wavelength, intensity, and pulse duration) with the physical properties of nanoparticles (size, shape, and composition) to form hitherto unrealized core-vest composite nanostructures (CVNs). Unlike typical core-shells, the plasmonic core of the resulting CVNs selectively maintains physical access to its surrounding. Tunable variations in local temperature profiles ≳50 °C are plasmonically induced over starburst-shaped nanoparticles as small as 50-100 nm. These temperature variations result in CVNs where the shell coverage mirrors the temperature variations. The precision thus offered individually tailors access pathways of the core and the shell.

  7. Optical enhancement of a printed organic tandem solar cell using diffractive nanostructures.

    PubMed

    Mayer, Jan A; Offermans, Ton; Chrapa, Marek; Pfannmöller, Martin; Bals, Sara; Ferrini, Rolando; Nisato, Giovanni

    2018-03-19

    Solution processable organic tandem solar cells offer a promising approach to achieve cost-effective, lightweight and flexible photovoltaics. In order to further enhance the efficiency of optimized organic tandem cells, diffractive light-management nanostructures were designed for an optimal redistribution of the light as function of both wavelength and propagation angles in both sub-cells. As the fabrication of these optical structures is compatible with roll-to-roll production techniques such as hot-embossing or UV NIL imprinting, they present an optimal cost-effective solution for printed photovoltaics. Tandem cells with power conversion efficiencies of 8-10% were fabricated in the ambient atmosphere by doctor blade coating, selected to approximate the conditions during roll-to-roll manufacturing. Application of the light management structure onto an 8.7% efficient encapsulated tandem cell boosted the conversion efficiency of the cell to 9.5%.

  8. Imparting biomolecules to a metal-organic framework material by controlled DNA tetrahedron encapsulation

    PubMed Central

    Jia, Yongmei; Wei, Benmei; Duan, Ruixue; Zhang, Ying; Wang, Boya; Hakeem, Abdul; Liu, Nannan; Ou, Xiaowen; Xu, Shaofang; Chen, Zhifei; Lou, Xiaoding; Xia, Fan

    2014-01-01

    Recently, the incorporation of biomolecules in Metal-organic frameworks (MOFs) attracts many attentions because of controlling the functions, properties and stability of trapped molecules. Although there are few reports on protein/MOFs composites and their applications, none of DNA/MOFs composite is reported, as far as we know. Here, we report a new composite material which is self-assembled from 3D DNA (guest) and pre-synthesized MOFs (host) by electrostatic interactions and hydrophilic interactions in a well-dispersed fashion. Its biophysical characterization is well analyzed by fluorescence spectroscopy, quartz crystal microbalance (QCM) and transmission electron microscopy (TEM). This new composite material keeps 3D DNA nanostructure more stable than only 3D DNA nanostructure in DI water at room temperature, and stores amounts of genetic information. It will make DNA as a guest for MOFs and MOFs become a new platform for the development of DNA nanotechnology. PMID:25090047

  9. Virus-Based Nanoparticles of Simian Virus 40 in the Field of Nanobiotechnology.

    PubMed

    Zhang, Wenjing; Zhang, Xian-En; Li, Feng

    2017-12-26

    Biomolecular nanostructures derived from living organisms, such as protein cages, fibers, and layers are drawing increasing interests as natural biomaterials. The virus-based nanoparticles (VNPs) of simian virus 40 (SV40), with a cage-like structure assembled from the major capsid protein of SV40, have been developed as a platform for nanobiotechnology in the recent decade. Foreign nanomaterials (e.g., quantum dots (QDs) and gold nanoparticles (AuNPs)) can be positioned in the inner cavity or on the outer surface of SV40 VNPs, through self-assembly by engineering the nanoparticle (NP)-protein interfacial interactions. Construction of these hybrid nanostructures has enabled integration of different functionalities. This review briefly summarizes the applications of SV40 VNPs in this multidisciplinary field, including NP encapsulation, templated assembly of nanoarchitectures, nanophotonics, and fluorescence imaging. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection.

    PubMed

    Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana; Borkar, Roshan M; Kumar, Jerald Mahesh; Kuncha, Madhusudana; Srinivas, R; Shyam Sunder, R; Sistla, Ramakrishna

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Assessment of mitochondrial membrane potential in HEI-OC1 and LLC-PK1 cells treated with gentamicin and mitoquinone.

    PubMed

    Ng, Maria Raye Anne V; Antonelli, Patrick J; Joseph, Jerin; Dirain, Carolyn Ojano

    2015-04-01

    To determine the effects of concurrent treatment with gentamicin and the mitochondria-targeted antioxidant mitoquinone (MitoQ; which may prevent gentamicin ototoxicity) on change in the mitochondrial membrane potential (Δψ(m)), a precursor of apoptosis. Prospective and controlled. Academic research laboratory. LLC-PK1 (Lilly Laboratories Culture-Pig Kidney Type 1) and HEI-OC1 (House Ear Institute Organ of Corti 1) cells-renal and auditory cell lines, respectively-were used in this study. Δψ(m) was assessed by flow cytometry through the MitoProbe JC-1 Kit for Flow Cytometry in untreated LLC-PK1 and HEI-OC1 cells and cells exposed to low- (100µM) or high- (2000µM) dose gentamicin for 24 hours, with and without 0.5µM each of MitoQ or idebenone (IDB; an untargeted ubiquinone). Δψ(m) was not different in untreated LLC-PK1 cells and cells coincubated with low-dose gentamicin and MitoQ or IDB (P > .05). In HEI-OC1 cells, coincubation with low-dose gentamicin and MitoQ decreased Δψ(m) (P = .002). Coincubation of LLC-PK1 cells with high-dose gentamicin and DMSO, MitoQ, or IDB depolarized Δψ(m) (P < .0001), with MitoQ depolarizing the Δψ(m) to a greater extent than that of IDB (P = .03). In contrast, HEI-OC1 cells demonstrated a hyperpolarized Δψ(m) when coincubated with high-dose gentamicin and DMSO, MitoQ, or IDB (P < .001). The combination of gentamicin and MitoQ holds the potential to disrupt Δψ(m). This suggests a heightened need to monitor for toxicity in patients receiving both agents. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  12. Gentamicin may have no effect on mortality of staphylococcal prosthetic valve endocarditis.

    PubMed

    Ramos-Martínez, Antonio; Muñoz Serrano, Alejandro; de Alarcón González, Arístides; Muñoz, Patricia; Fernández-Cruz, Ana; Valerio, Maricela; Fariñas, María Carmen; Gutiérrez-Cuadra, Manuel; Miró, José Ma; Ruiz-Morales, Josefa; Sousa-Regueiro, Dolores; Montejo, José Miguel; Gálvez-Acebal, Juan; HidalgoTenorio, Carmen; Domínguez, Fernando

    2018-07-01

    To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84-11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03-6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29-3.38) in the multivariable analysis. The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome. Copyright © 2018. Published by Elsevier Ltd.

  13. Gentamicin modified chitosan film with improved antibacterial property and cell biocompatibility.

    PubMed

    Liu, Yang; Ji, Peihong; Lv, Huilin; Qin, Yong; Deng, Linhong

    2017-05-01

    Gentamicin modified chitosan film (CS-GT) was produced using a three-step procedure comprising: (i) the chitosan solution was air-dried to form a chitosan (CS) film, (ii) using citric acid to generate the amide and carboxyl groups on the surface of CS, (iii) the CS with surface carboxyl groups was modified by grafting of gentamicin. After modification, this CS-GT film has excellent hydrophilicity and biocompatibility. It is very evident that the gentamicin grafting treatment significantly improves the antibacterial properties of the CS film. Our preliminary results suggest that this novel gentamicin modified chitosan film, which can be prepared in large quantities and at low cost, should have potential application in biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 3D-nanostructured boron-doped diamond for microelectrode array neural interfacing.

    PubMed

    Piret, Gaëlle; Hébert, Clément; Mazellier, Jean-Paul; Rousseau, Lionel; Scorsone, Emmanuel; Cottance, Myline; Lissorgues, Gaelle; Heuschkel, Marc O; Picaud, Serge; Bergonzo, Philippe; Yvert, Blaise

    2015-06-01

    The electrode material is a key element in the design of long-term neural implants and neuroprostheses. To date, the ideal electrode material offering high longevity, biocompatibility, low-noise recording and high stimulation capabilities remains to be found. We show that 3D-nanostructured boron doped diamond (BDD), an innovative material consisting in a chemically stable material with a high aspect ratio structure obtained by encapsulation of a carbon nanotube template within two BDD nanolayers, allows neural cell attachment, survival and neurite extension. Further, we developed arrays of 20-μm-diameter 3D-nanostructured BDD microelectrodes for neural interfacing. These microelectrodes exhibited low impedances and low intrinsic recording noise levels. In particular, they allowed the detection of low amplitude (10-20 μV) local-field potentials, single units and multiunit bursts neural activity in both acute whole embryonic hindbrain-spinal cord preparations and long-term hippocampal cell cultures. Also, cyclic voltammetry measurements showed a wide potential window of about 3 V and a charge storage capacity of 10 mC.cm(-2), showing high potentiality of this material for neural stimulation. These results demonstrate the attractiveness of 3D-nanostructured BDD as a novel material for neural interfacing, with potential applications for the design of biocompatible neural implants for the exploration and rehabilitation of the nervous system. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. On the Enhanced Antibacterial Activity of Antibiotics Mixed with Gold Nanoparticles

    NASA Astrophysics Data System (ADS)

    Burygin, G. L.; Khlebtsov, B. N.; Shantrokha, A. N.; Dykman, L. A.; Bogatyrev, V. A.; Khlebtsov, N. G.

    2009-08-01

    The bacterial action of gentamicin and that of a mixture of gentamicin and 15-nm colloidal-gold particles on Escherichia coli K12 was examined by the agar-well-diffusion method, enumeration of colony-forming units, and turbidimetry. Addition of gentamicin to colloidal gold changed the gold color and extinction spectrum. Within the experimental errors, there were no significant differences in antibacterial activity between pure gentamicin and its mixture with gold nanoparticles (NPs). Atomic absorption spectroscopy showed that upon application of the gentamicin-particle mixture, there were no gold NPs in the zone of bacterial-growth suppression in agar. Yet, free NPs diffused into the agar. These facts are in conflict with the earlier findings indicating an enhancement of the bacterial activity of similar gentamicin-gold nanoparticle mixtures. The possible causes for these discrepancies are discussed, and the suggestion is made that a necessary condition for enhancement of antibacterial activity is the preparation of stable conjugates of NPs coated with the antibiotic molecules.

  16. Drug delivery using novel nanoplexes against a Salmonella mouse infection model

    NASA Astrophysics Data System (ADS)

    Ranjan, A.; Pothayee, N.; Seleem, M.; Jain, N.; Sriranganathan, N.; Riffle, J. S.; Kasimanickam, R.

    2010-03-01

    A novel methodology for incorporating gentamicin into macromolecular complexes with anionic homo- and block copolymers via cooperative electrostatic interactions is described. Block copolymers of poly(ethylene oxide- b-sodium acrylate) (PEO- b-PAA- +Na) or poly(ethylene oxide- b-sodium methacrylate) (PEO- b-PMA- +Na) were blended with PAA- Na+ and complexed with the polycationic antibiotic gentamicin. Gentamicin nanoplexes made with PEO- b-PMA- +Na/PAA- +Na (PMPG) and analogous nanoplexes with PEO- b-PAA- +Na/PAA- +Na (PAPG) had mean intensity average diameters of 120 and 90 nm, zeta potentials of -17 and -11 mv, and incorporated 26% and 23% by weight of gentamicin, respectively. Gentamicin release rates at physiological pH from nanoplexes were relatively slow. PAPG and PMPG as drug delivery systems for treating murine salmonellosis at doses similar to the free gentamicin experiments resulted in reduced numbers of viable bacteria in the liver and spleen. Polymeric nanoplexes developed by this methodology can potentially improve targeting of intracellular pathogens.

  17. Gentamicin-Loaded Thermosetting Hydrogel and Moldable Composite Scaffold: Formulation Study and Biologic Evaluation.

    PubMed

    Dorati, Rossella; De Trizio, Antonella; Genta, Ida; Merelli, Alessia; Modena, Tiziana; Conti, Bice

    2017-06-01

    The aim was to design biodegradable drug delivery systems for gentamicin local delivery, meanwhile acting as scaffold for bone regeneration. Gentamicin-loaded thermosetting composite hydrogels were prepared combining chitosan with bovine bone substitutes (Orthoss® granules), beta-glycerophosphate as cross-linker, and lyophilized to obtain moldable composite scaffolds (moldable composite scaffold loaded with gentamicin [mCSG]). Diverse techniques for gentamicin loading into mCS were investigated by drug incorporation during hydrogel preparation or drug absorption on preformed mCS. Rheologic hydrogel characterization was performed. mCSGs were characterized for porosity, stability (water retention, water uptake), gentamicin release, cell seeding and proliferation, and antimicrobial effect on Escherichia coli ATCC 10356. Results show suitable gentamicin loadings were 4 mg in 1 mL thermosetting composite hydrogel starting solution, irreversible hydrogel thermosetting behavior, and cosolute effect of gentamicin on sol-gel transition. Positive results in terms of porosity (80%-86%), scaffold water uptake, and retention capability were obtained. Antibiotic in vitro release was completed in 4 h. Good cell seeding results were observed for mCSG1-5; mCSG3 and mCSG5 resulted the best as cell proliferation results. mCSG exerted bactericidal effect for 24 h, with superimposition of chitosan bacteriostatic effect in the first 4 h. The results lead to consider the drug delivery for reducing infection risk during bone open surgeries. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Is gentamicin ototoxic to the fetus?

    PubMed

    Kirkwood, Allison; Harris, Connie; Timar, Niki; Koren, Gideon

    2007-02-01

    Gentamicin is used in pregnancy to treat infections that cause complications to the mother and fetus if left untreated. In 2003, Schering, the manufacturer of Garamycin Injectable, amended the product monograph in the Compendium of Pharmaceuticals and Specialties to state that gentamicin should be avoided in pregnancy due to cases of "total irreversible bilateral congenital deafness" in babies exposed to gentamicin in utero. Because we have identified, after an intensive literature search, only two cases over many years of availability, it is questionable whether the outcome can be attributed to drug use rather than other factors. The main objective of this study was to determine whether any infant exposed in utero to intravenous gentamicin and born between January 2002 and April 2006 at Victoria General Hospital demonstrated audiologic deficits on routine hearing testing. Such testing has been universally available since late 2001. Our secondary objectives were to examine patterns of gentamicin use, including indication, dosage, duration, and to determine whether or not monitoring of serum gentamicin levels was done. Women who had received gentamicin were identified through pharmacy records and their charts reviewed for factors that might contribute to fetal deafness including substance abuse, use of other potentially ototoxic medications, genetic predisposition, and intrauterine infections. We reviewed audiology test result and the infants' charts for potential confounding factors, including prematurity, low birth weight, low Apgar scores, anoxia, hyperbilirubinemia, sepsis, and meningitis. Fifty-two charts were reviewed, 40 of which documented live births. There was no case of hearing loss documented. Of the eight fetal losses, six (11.5%) were preterm births before viability, and two were elective terminations. Pyelonephritis was the main indication for gentamicin use (48%), followed by chorioamnionitis (31%) and other miscellaneous indications (21%). Three times daily dosing was used for a mean duration of 2.7 +- 2.3 days, resulting in an average cumulative dose of 764 +- 600 mg gentamicin. The average gestational age at exposure was 28 weeks. Maternal serum gentamicin levels were obtained in 72.5% of cases, and no trough level was above 2 mg/L. Other potentially ototoxic medications were administered to the mother in 17.5% of pregnancies, and to 17.5% of babies in the immediate newborn period. With the exception of one infant who died before additional testing could be carried out, all the infants passed hearing tests, 89% on initial screening. In utero exposure to gentamicin did not cause an increase in audiologic impairment in the infants tested in this cohort.

  19. Neurobiochemical changes in the vicinity of a nanostructured neural implant

    NASA Astrophysics Data System (ADS)

    Bérces, Zsófia; Tóth, Kinga; Márton, Gergely; Pál, Ildikó; Kováts-Megyesi, Bálint; Fekete, Zoltán; Ulbert, István; Pongrácz, Anita

    2016-10-01

    Neural interface technologies including recording and stimulation electrodes are currently in the early phase of clinical trials aiming to help patients with spinal cord injuries, degenerative disorders, strokes interrupting descending motor pathways, or limb amputations. Their lifetime is of key importance; however, it is limited by the foreign body response of the tissue causing the loss of neurons and a reactive astrogliosis around the implant surface. Improving the biocompatibility of implant surfaces, especially promoting neuronal attachment and regeneration is therefore essential. In our work, bioactive properties of implanted black polySi nanostructured surfaces (520-800 nm long nanopillars with a diameter of 150-200 nm) were investigated and compared to microstructured Si surfaces in eight-week-long in vivo experiments. Glial encapsulation and local neuronal cell loss were characterised using GFAP and NeuN immunostaining respectively, followed by systematic image analysis. Regarding the severity of gliosis, no significant difference was observed in the vicinity of the different implant surfaces, however, the number of surviving neurons close to the nanostructured surface was higher than that of the microstructured ones. Our results imply that the functionality of implanted microelectrodes covered by Si nanopillars may lead to improved long-term recordings.

  20. Characterization and analysis of thermoelectric transport using SPB model in nanostructured aluminum doped zinc tellurium

    NASA Astrophysics Data System (ADS)

    Bhaskar, Ankam; Pai, Yi-Hsuan; Liu, Chia-Jyi

    2017-11-01

    Low-temperature electronic and thermal transport measurements are carried out on nanostructured Zn1-x Al x Te (0  ⩽  x  ⩽  0.15) fabricated using hydrothermal synthesis followed by evacuated-and-encapsulated sintering. A single parabolic band with acoustic phonon scattering is used to analyze thermoelectric transport data. It is found that reduced Fermi energy gets closer to the valence band edge and density of states effective mass, effective density of states, and Hall factor decrease with increasing x in doped samples. The chemical carrier concentration, carrier density independent mobility, β, and theoretical zT values increase with increasing x in doped samples. The nanostructured Zn1-x Al x Te exhibits significant reduction of thermal conductivity at 300 K (1.82-3.71 W m-1 K-1) as compared to bulk ZnTe (18 W m-1 K-1). The point-defect scattering and phonon-grain scattering play an important role in reducing the lattice thermal conductivity. In addition, partial substitution of Al3+ for Zn2+ significantly improves both the power factor and zT values.

  1. 21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

  2. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

  3. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

  4. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

  5. 21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

  6. 21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

  7. 21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

  8. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

  9. 21 CFR 524.1132 - Hydrocortisone aceponate, miconazole nitrate, gentamicin sulfate otic suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Hydrocortisone aceponate, miconazole nitrate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1132 Hydrocortisone aceponate, miconazole nitrate, gentamicin... (mg) of hydrocortisone aceponate, 15.1 mg of miconazole nitrate, and 1,505 micrograms of gentamicin...

  10. 21 CFR 524.1132 - Hydrocortisone, miconazole, and gentamicin otic suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Hydrocortisone, miconazole, and gentamicin otic... NEW ANIMAL DRUGS § 524.1132 Hydrocortisone, miconazole, and gentamicin otic suspension. (a) Specifications. Each milliliter (mL) of suspension contains 1.11 milligrams (mg) of hydrocortisone aceponate, 15...

  11. 21 CFR 524.1132 - Hydrocortisone aceponate, miconazole nitrate, gentamicin sulfate otic suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Hydrocortisone aceponate, miconazole nitrate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1132 Hydrocortisone aceponate, miconazole nitrate, gentamicin... (mg) of hydrocortisone aceponate, 15.1 mg of miconazole nitrate, and 1,505 micrograms of gentamicin...

  12. Gentamicin in the Clinical Setting

    ERIC Educational Resources Information Center

    Pillers, De-Ann M.; Schleiss, Mark R.

    2005-01-01

    Gentamicin is an aminoglycoside antibiotic that has been a mainstay in pediatric care for decades. Although new antibiotics are constantly under development, gentamicin continues to play an important role in clinical medicine. Although this may be surprising in the context of evidence of an association with hearing loss, both on a toxicity and a…

  13. Determination of Gentamicin Sulphate Composition and Related Substances in Pharmaceutical Preparations by LC with Charged Aerosol Detection

    PubMed Central

    Stypulkowska, Karolina; Fijalek, Zbigniew; Sarna, Katarzyna

    2010-01-01

    A new, simple and repeatable liquid chromatography method with charged aerosol detection (LC-CAD) for the determination of gentamicin sulphate composition and related substances has been developed. Gentamicin lacks of chromophores, therefore its determination is quite problematic. Using a universal CAD enables to achieve good separation without sample derivatization. Mass spectrometry was employed to confirm the LC-CAD peak profile. The proposed method was validated and applied for the determination of gentamicin sulphate composition and related substances in pharmaceutical preparations. PMID:21212825

  14. A comparison of netilmicin and gentamicin in the treatment of pelvic infections.

    PubMed

    Schnider, G; Birken, R A; Poindexter, A N

    1979-11-01

    Seventy-five women admitted with the symptom complex suggestive of pelvic inflammatory disease( PID) were started on a penicillin-aminoglycoside antibiotic regimen. An aminoglycoside, gentamicin or netilmicin (Schering-Plough), was chosen randomly and given parenterally. Forty-two patients received netilmicin and 33 received gentamicin for 5 days. Therapeutic response to the 2 antibiotic regimens was similar. Aminoglycosides have been associated with both nephrotoxicity and ototoxicity. Blood chemistries were studied in all patients. The only manifested toxicity was in 2 patients treated with gentamicin. Endometrial-endocervical cultures were obtained before and after therapy. The microbacteria isolated by standard culture techniques before therapy revealed Neisseria gonorrhoeae in 69% and 51% of the netilmicin and gentamicin groups, respectively; anaerobic organisms were cultured in about 75% of each group.

  15. Intra-articular implantation of gentamicin impregnated collagen sponge causes joint inflammation and impaired renal function in dogs.

    PubMed

    Hayes, Galina; Gibson, Tom; Moens, Noel M M; Nykamp, Stephanie; Wood, Darren; Foster, Robert; Lerer, Asaf

    2016-01-01

    Gentamicin impregnated collagen sponge (GICS) can be used to treat intra-articular surgical site infections. High local concentrations of gentamicin can be reached for short periods; however the collagen vehicle may persist for much longer periods. We wished to determine the effect of sponge implantation on joint inflammation and renal function. Eighteen medium sized mixed breed research dogs of hound type were randomized to two groups; arthroscopic implantation of GICS at gentamicin dose = 6 mg/kg (n = 9) or sham operation (n = 9). Endpoints consisted of joint inflammation measured by synovial fluid cell counts and cytokine concentrations; lameness measured by force plate asymmetry indices; and renal function measured by glomerular filtration rate (GFR) study. The prevalence of lesions associated with aminoglycoside nephrotoxicity was assessed by renal biopsy and transmission electron microscopy. Gentamicin impregnated collagen sponge implantation caused joint inflammation (p <0.01), lameness (p = 0.04), and decreased GFR (p = 0.04). No difference was observed in the prevalence of renal lesions on biopsy between the treatment and control groups (p = 0.49). Gentamicin impregnated collagen sponge implantation causes joint inflammation and lameness as well as GFR reductions at the dose assessed. Gentamicin impregnated collagen sponge are not recommended for intra-articular implantation in dogs.

  16. Round window administration of gentamicin: a new method for the study of ototoxicity of cochlear hair cells.

    PubMed

    Husmann, K R; Morgan, A S; Girod, D A; Durham, D

    1998-11-01

    Damage to inner ear sensory hair cells after systemic administration of ototoxic drugs has been documented in humans and animals. Birds have the ability to regenerate new hair cells to replace those damaged by drugs or noise. Unfortunately, the systemic administration of gentamicin damages both ears in a variable fashion with potentially confounding systemic drug effects. We developed a method of direct application of gentamicin to one cochlea of hatchling chickens, allowing the other ear to serve as a within-animal control. We tested variables including the vehicle for application, location of application, dosage, and duration of gentamicin exposure. After 5 or 28 days survival, the percent length damage to the cochlea and regeneration of hair cells was evaluated using scanning electron microscopy. Controls consisted of the opposite unexposed cochlea and additional animals which received saline instead of gentamicin. Excellent damage was achieved using gentamicin-soaked Gelfoam pledgets applied to the round window membrane. The percent length damage could be varied from 15 to 100% by changing the dosage of gentamicin, with exposures as short as 30 min. No damage was observed in control animals. Regeneration of hair cells was observed in both the base and apex by 28 days survival.

  17. Prevention of hepatic and renal toxicity with bradykinin potentiating factor (BPF) isolated from Egyptian scorpion venom (Buthus occitanus) in gentamicin treated rats.

    PubMed

    Bekheet, Souad H M; Awadalla, Eatemaad A; Salman, Muhammad M; Hassan, Mohamed K

    2013-04-01

    The present investigation report the effect of a bradykinin-potentiating factor (BPF) on gentamicin-induced oxidative stress in rat liver and kidney. BPF is a peptide fraction isolated from the venom of the Egyptian scorpion (Buthus occitanus) has been demonstrated to have antioxidant, free radical scavenger and anti-inflammatory effects. Thirty male Rattus norvegicus (130-150 g) were included and divided into three equal groups as follows: Group I (control), group II was (ip) injected with gentamicin alone (80 mg/kg/day) for 15 days, group III was given (ip) injection of BPF (1mg/kg/day) one hour prior to gentamicin treatment for 15 days with the same dose of gentamicin as group II. Both organs were subjected to histopathological analysis with the light microscope. The activities of alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphatase (ALP) in serum were measured as indicators of the liver function. As parameters of the kidney function, creatinine, uric acid and urea concentrations were determined. Also, malondialdehyde (MDA), reduced glutathione (GSH), super oxide dismutase (SOD) and catalase (CAT) were determined in both tissues. Gentamicin caused a significant decrease or inhibition in the activities of GSH, SOD, and CAT, with significant increase in the level of MDA, ALT, AST, ALP, as well as creatinine, uric acid and urea concentrations in versus to control groups in both liver and kidney. Co-administration of gentamicin and BPF significantly increased the activity of GSH, SOD, and CAT, with significant decrease in the level of MDA and maintained serum (ALT); (AST); (ALP), creatinine, uric acid and urea concentrations as the same level as control group. Moreover, administration of gentamicin resulted in damage to liver and kidney structures. Administration of BPF before gentamicin exposure prevented severe alterations of biochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with BPF significantly attenuated the physiological and histopathological alterations induced by gentamicin. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs dysfunctions and diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. In-vitro bioactivity and electrochemical behavior of polyaniline encapsulated titania nanotube arrays for biomedical applications

    NASA Astrophysics Data System (ADS)

    Agilan, P.; Rajendran, N.

    2018-05-01

    Titania nanotube arrays (TNTA) have attracted increasing attention due to their outstanding properties and potential applications in biomedical field. Fabrication of titania nanotubes on titanium surface enhances the biocompatibility. Polyaniline (PANI) is one of the best conducting polymers with remarkable corrosion resistance and reasonable biocompatibility. In this work, the corrosion resistance and biocompatibility of polyaniline encapsulated TiO2 nanotubes for orthopaedic applications were investigated. The vertically oriented, highly ordered TiO2 nanotubes were fabricated on titanium by electrochemical anodization process using fluoride containing electrolytes. The anodization parameters viz., voltage, pH, time and electrolyte concentration were optimized to get orderly arranged TNTA. Further, the conducting polymer PANI was encapsulated on TNTA by electropolymerization process to enhance the corrosion resistance. The nanostructure of the fabricated TNTA and polyaniline encapsulated titania nanotube arrays (PANI-TNTA) were investigated by HR SEM analysis. The formed phases and functional groups were find using XRD, ATR-FTIR. The hydrophilic surface of TNTA and PANI-TNTA was identified by water contact angle studies. The corrosion behavior of specimens was evaluated by electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization studies. In-vitro immersion studies were carried out in simulated body fluid solution (Hanks' solution) to evaluate the bioactivity of the TNTA and PANI-TNTA. The surface morphological studies revealed the formation of PANI on the TNTA surface. Formation of hydroxyapatite (HAp) on the surfaces of TNTA and PANI-TNTA enhanced the bioactivity and corrosion resistance.

  19. Sub-inhibitory concentrations of gentamicin triggers the expression of aac(6')Ie-aph(2″)Ia, chaperons and biofilm related genes in Lactobacillus plantarum MCC 3011.

    PubMed

    George, Jaimee; Halami, Prakash Motiram

    2017-10-01

    The study aimed to analyze the effects of sub-inhibitory concentrations of gentamicin on the expressions of high level aminoglycoside resistant (HLAR) bifunctional aac(6')Ie-aph(2″)Ia, biofilm and chaperone genes in Lactobacillus plantarum. The analysis of the biofilm formation in five isolates obtained from chicken sausages indicated their role in exhibiting phenotypic resistance based on the varied MIC values despite carrying the bifunctional gene. The biofilm formation significantly increased when L. plantarum MCC 3011 was grown in sub-inhibitory concentrations of gentamicin (4 μg/ml), kanamycin (8 μg/ml) and streptomycin (2 μg/ml). Thirty day gentamicin selection increased minimum inhibitory concentration (MIC) values from 4 to 64 and 2 to 256 fold for gentamicin and kanamycin, respectively when compared to the parental cultures. Expression studies revealed that constant exposure to gentamicin had induced chaperon [groEL] and the bifunctional gene, aac(6')Ie-aph(2″)Ia upto nine fold. Induction of groEL, groES and lamC genes in gentamicin (4 μg/ml) preincubated MCC 3011 indicated their significant role in aminoglycoside mediated response. Our study indicates that constant exposure to sub inhibitory concentrations of gentamicin allows L. plantarum to adapt against higher doses of aminoglycosides. This highlights the risks and food safety issues associated with the use of aminoglycosides in livestock and consumption of farm oriented fermented food products. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  20. Food Antimicrobials Nanocarriers

    PubMed Central

    Blanco-Padilla, Adriana; Soto, Karen M.; Hernández Iturriaga, Montserrat

    2014-01-01

    Natural food antimicrobials are bioactive compounds that inhibit the growth of microorganisms involved in food spoilage or food-borne illness. However, stability issues result in degradation and loss of antimicrobial activity. Nanoencapsulation allows protection of antimicrobial food agents from unfavorable environmental conditions and incompatibilities. Encapsulation of food antimicrobials control delivery increasing the concentration of the antimicrobials in specific areas and the improvement of passive cellular absorption mechanisms resulted in higher antimicrobial activity. This paper reviews the present state of the art of the nanostructures used as food antimicrobial carriers including nanoemulsions, nanoliposomes, nanoparticles, and nanofibers. PMID:24995363

  1. Modification of polyelectrolyte microcapsules into a container for the low molecular weight compounds

    NASA Astrophysics Data System (ADS)

    Goryacheva, O. A.; Gao, H.; Sukhorukov, G. B.

    2018-04-01

    Polyelectrolyte microcapsules are one of the most successful developments in the direction of target drug delivery. Nevertheless, to encapsulate low molecular weight compounds and to deliver the targeted drugs it is necessary to modify the surface of the microcapsules. Silica nanostructures obtained as result of hydrolysis of (3-Aminopropyl)- triethoxysilane (APTES) were used for the modification of the microcapsules. This material shows no toxic effect on cells and is capable of biodegradation. Amino-groups in the structure of APTES make it possible for further direct bioconjugation.

  2. Alternating Mupirocin/Gentamicin is Associated with Increased Risk of Fungal Peritonitis as Compared with Gentamicin Alone - Results of a Randomized Open-Label Controlled Trial.

    PubMed

    Wong, Ping-Nam; Tong, Gensy M W; Wong, Yuk-Yi; Lo, Kin-Yee; Chan, Shuk-Fan; Lo, Man-Wai; Lo, Kwok-Chi; Ho, Lo-Yi; Tse, Cindy W S; Mak, Siu-Ka; Wong, Andrew K M

    2016-01-01

    ♦ Catheter-related infection, namely exit-site infection (ESI) and peritonitis, is a major infectious complication and remains a main cause of technique failure for patients receiving peritoneal dialysis (PD). Topical application of antibiotic cream might reduce catheter-related infection but emergence of resistant or opportunistic organisms could be a concern. Optimal topical agents and regimens remain to be determined. We did a study to examine the effect of an alternating topical antibiotic regimen in preventing catheter-related infection. ♦ We performed a single-center, randomized, open-label study to compare daily topical application of gentamicin cream with a gentamicin/mupirocin alternate regimen to the exit site. Patients randomized to alternating regimen were asked to have daily application of gentamicin cream in odd months and mupirocin cream in even months. Primary outcomes were ESI and peritonitis. Secondary outcomes were catheter removal or death caused by catheter-related infection. A total of 146 patients (71, gentamicin group; 75, alternating regimen group) were enrolled with a total follow-up duration of 174 and 181 patient-years for gentamicin and alternating groups, respectively. All patients were followed up until catheter removal, death, transfer to another unit, transplantation or the end of the study on March 31, 2014. There were no significant differences in the age, sex, dialysis vintage, and rate of diabetes, helper-assisted dialysis and methicillin-resistant Staphylococcus aureus (MRSA) carriage state. ♦ No difference was seen in the time to first ESI or peritonitis. However, the time to first gram-negative peritonitis seemed longer for the gentamicin group (p = 0.055). The 2 groups showed a similar rate of ESI (0.17/yr vs 0.19/yr, p = 0.93) but P. aeruginosa ESI was less common in the gentamicin group (0.06/yr vs 0.11/yr, p < 0.001). There was no difference in the incidence of ESI due to non-tuberculous mycobacteria. Peritonitis rate was significantly lower in the gentamicin group (0.22/yr vs 0.32/yr, p < 0.001), with a striking decrease in gram-negative peritonitis (0.08/yr vs 0.14/yr, p < 0.001), and fungal peritonitis (0.006/yr vs 0.03/yr, p < 0.001), which was all antibiotics-related episodes with antecedent use of systemic antibiotics for the treatment of catheter-related infections. There was no significant difference in the catheter loss or death related to catheter-related infection. ♦ Alternating gentamicin/mupirocin cream application appeared as effective as gentamicin alone in preventing ESI except for P. aeruginosa. However, it was inferior to gentamicin in the prevention of peritonitis episodes, especially for those caused by gram-negative organisms. It was also not useful in reducing catheter-related infection due to opportunistic organisms but instead associated with a higher incidence of antibiotic-related fungal peritonitis. Copyright © 2016 International Society for Peritoneal Dialysis.

  3. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1044 Gentamicin...

  4. 21 CFR 520.1044c - Gentamicin sulfate powder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate powder. 520.1044c Section 520.1044c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1044c Gentamicin...

  5. 21 CFR 556.300 - Gentamicin sulfate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... million in fat and kidney. A microbiological determinative procedure and an HPLC confirmatory procedure for gentamicin have been developed to assay gentamicin in kidney at 0.4 ppm. Since residues of... concentration of 0.4 ppm in kidney corresponds to 0.4 ppm of total residue. [48 FR 791, Jan. 7, 1983, as amended...

  6. 21 CFR 556.300 - Gentamicin sulfate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... million in fat and kidney. A microbiological determinative procedure and an HPLC confirmatory procedure for gentamicin have been developed to assay gentamicin in kidney at 0.4 ppm. Since residues of... concentration of 0.4 ppm in kidney corresponds to 0.4 ppm of total residue. [48 FR 791, Jan. 7, 1983, as amended...

  7. 21 CFR 520.1044b - Gentamicin sulfate pig pump oral solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate pig pump oral solution. 520....1044b Gentamicin sulfate pig pump oral solution. (a) Specifications. Each milliliter of pig pump oral.... (d) Conditions of use—(1) Amount. Administer 1.15 milliliters of pig pump oral solution (5 milligrams...

  8. 21 CFR 520.1044b - Gentamicin sulfate pig pump oral solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate pig pump oral solution. 520....1044b Gentamicin sulfate pig pump oral solution. (a) Specifications. Each milliliter of pig pump oral.... (d) Conditions of use—(1) Amount. Administer 1.15 milliliters of pig pump oral solution (5 milligrams...

  9. 21 CFR 520.1044b - Gentamicin sulfate pig pump oral solution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate pig pump oral solution. 520....1044b Gentamicin sulfate pig pump oral solution. (a) Specifications. Each milliliter of pig pump oral.... (d) Conditions of use—(1) Amount. Administer 1.15 milliliters of pig pump oral solution (5 milligrams...

  10. 21 CFR 520.1044b - Gentamicin sulfate pig pump oral solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate pig pump oral solution. 520....1044b Gentamicin sulfate pig pump oral solution. (a) Specifications. Each milliliter of pig pump oral.... (d) Conditions of use—(1) Amount. Administer 1.15 milliliters of pig pump oral solution (5 milligrams...

  11. 21 CFR 520.1044b - Gentamicin sulfate pig pump oral solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate pig pump oral solution. 520....1044b Gentamicin sulfate pig pump oral solution. (a) Specifications. Each milliliter of pig pump oral.... (d) Conditions of use—(1) Amount. Administer 1.15 milliliters of pig pump oral solution (5 milligrams...

  12. Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria.

    PubMed

    Lee, Wee Xian; Basri, Dayang Fredalina; Ghazali, Ahmad Rohi

    2017-03-17

    The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5) against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923 , Escherichia coli O157 and Pseudomonas aeruginosa 15442 . However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents.

  13. Prevention of gentamicin ototoxicity with N-acetylcysteine and vitamin A.

    PubMed

    Aladag, I; Guven, M; Songu, M

    2016-05-01

    To investigate the use of systemic N-acetylcysteine and vitamin A in the prevention of gentamicin ototoxicity in rats. Forty-two Wistar rats were divided into four groups according to treatment: intratympanic saline, intratympanic gentamicin, intraperitoneal vitamin A after intratympanic gentamicin, and intraperitoneal N-acetylcysteine after intratympanic gentamicin. Signal-to-noise ratio and distortion product otoacoustic emissions were evaluated in all groups. N-acetylcysteine had a significant protective effect at 1.5, 2, 3, 4, 6 and 8 kHz, whilst vitamin A had a significant protective effect at 2, 3, 4 and 6 kHz, as determined by the distortion product otoacoustic emission measurements. According to the signal-to-noise measurements, N-acetylcysteine had a significant protective effect at 1.5, 2, 3, 4, 6 and 8 kHz, whilst vitamin A had a significant protective effect at 3, 6 and 8 kHz. Gentamicin-induced hearing loss in rats may be prevented by the concomitant use of vitamin A and N-acetylcysteine. Specifically, N-acetylcysteine appeared to have a more protective effect than vitamin A for a greater range of noise frequencies.

  14. Chitosan Improves Anti-Biofilm Efficacy of Gentamicin through Facilitating Antibiotic Penetration

    PubMed Central

    Mu, Haibo; Guo, Fan; Niu, Hong; Liu, Qianjin; Wang, Shunchun; Duan, Jinyou

    2014-01-01

    Antibiotic overuse is one of the major drivers in the generation of antibiotic resistant “super bugs” that can potentially cause serious effects on health. In this study, we reported that the polycationic polysaccharide, chitosan could improve the efficacy of a given antibiotic (gentamicin) to combat bacterial biofilms, the universal lifestyle of microbes in the world. Short- or long-term treatment with the mixture of chitosan and gentamicin resulted in the dispersal of Listeria monocytogenes (L. monocytogenes) biofilms. In this combination, chitosan with a moderate molecular mass (~13 kDa) and high N-deacetylation degree (~88% DD) elicited an optimal anti-biofilm and bactericidal activity. Mechanistic insights indicated that chitosan facilitated the entry of gentamicin into the architecture of L. monocytogenes biofilms. Finally, we showed that this combination was also effective in the eradication of biofilms built by two other Listeria species, Listeria welshimeri and Listeria innocua. Thus, our findings pointed out that chitosan supplementation might overcome the resistance of Listeria biofilms to gentamicin, which might be helpful in prevention of gentamicin overuse in case of combating Listeria biofilms when this specific antibiotic was recommended. PMID:25479075

  15. Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats.

    PubMed

    Diefenbeck, M; Schrader, C; Gras, F; Mückley, T; Schmidt, J; Zankovych, S; Bossert, J; Jandt, K D; Völpel, A; Sigusch, B W; Schubert, H; Bischoff, S; Pfister, W; Edel, B; Faucon, M; Finger, U

    2016-09-01

    Implant related infection is one of the most feared and devastating complication associated with the use of orthopaedic implant devices. Development of anti-infective surfaces is the main strategy to prevent implant contamination, biofilm formation and implant related osteomyelitis. A second concern in orthopaedics is insufficient osseointegration of uncemented implant devices. Recently, we reported on a macroporous titanium-oxide surface (bioactive TiOB) which increases osseointegration and implant fixation. To combine enhanced osseointegration and antibacterial function, the TiOB surfaces were, in addition, modified with a gentamicin coating. A rat osteomyelitis model with bilateral placement of titanium alloy implants was employed to analyse the prophylactic effect of gentamicin-sodiumdodecylsulfate (SDS) and gentamicin-tannic acid coatings in vivo. 20 rats were randomly assigned to four groups: (A) titanium alloy; PBS inoculum (negative control), (B) titanium alloy, Staphylococcus aureus inoculum (positive control), (C) bioactive TiOB with gentamicin-SDS and (D) bioactive TiOB plus gentamicin-tannic acid coating. Contamination of implants, bacterial load of bone powder and radiographic as well as histological signs of implant-related osteomyelitis were evaluated after four weeks. Gentamicin-SDS coating prevented implant contamination in 10 of 10 tibiae and gentamicin-tannic acid coating in 9 of 10 tibiae (infection prophylaxis rate 100% and 90% of cases, respectively). In Group (D) one implant showed colonisation of bacteria (swab of entry point and roll-out test positive for S. aureus). The interobserver reliability showed no difference in the histologic and radiographic osteomyelitis scores. In both gentamicin coated groups, a significant reduction of the histological osteomyelitis score (geometric mean values: C = 0.111 ± 0.023; D = 0.056 ± 0.006) compared to the positive control group (B: 0.244 ± 0.015; p < 0.05) was observed. The radiographic osteomyelitis scores confirmed these histological findings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

    PubMed Central

    Floquet, Célia; Hatin, Isabelle; Rousset, Jean-Pierre; Bidou, Laure

    2012-01-01

    The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable. PMID:22479203

  17. Fosfomycin Addition to Poly(D,L-Lactide) Coating Does Not Affect Prophylaxis Efficacy in Rat Implant-Related Infection Model, But That of Gentamicin Does

    PubMed Central

    Yorukoglu, Ali Cagdas; Kaleli, Ilknur; Bir, Ferda

    2016-01-01

    Gentamicin is the preferred antimicrobial agent used in implant coating for the prevention of implant-related infections (IRI). However, the present heavy local and systemic administration of gentamicin can lead to increased resistance, which has made its future use uncertain, together with related preventive technologies. Fosfomycin is an alternative antimicrobial agent that lacks the cross-resistance presented by other classes of antibiotics. We evaluated the efficacy of prophylaxis of 10% fosfomycin-containing poly(D,L-lactide) (PDL) coated K-wires in a rat IRI model and compared it with uncoated (Control 1), PDL-coated (Control 2), and 10% gentamicin-containing PDL-coated groups with a single layer of coating. Stainless steel K-wires were implanted and methicillin-resistant Staphylococcus aureus (ATCC 43300) suspensions (103 CFU/10 μl) were injected into a cavity in the left tibiae. Thereafter, K-wires were removed and cultured in tryptic soy broth and then 5% sheep blood agar mediums. Sliced sections were removed from the tibiae, stained with hematoxylin-eosin, and semi-quantitatively evaluated with X-rays. The addition of fosfomycin into PDL did not affect the X-ray and histopathological evaluation scores; however, the addition of gentamicin lowered them. The addition of gentamicin showed a protective effect after the 28th day of X-ray evaluations. PDL-only coating provided no protection, while adding fosfomycin to PDL offered a 20% level protection and adding gentamicin offered 80%. Furthermore, there were 103 CFU level growths in the gentamicin-added group, while the other groups had 105. Thus, the addition of fosfomycin to PDL does not affect the efficacy of prophylaxis, but the addition of gentamicin does. We therefore do not advise the use of fosfomycin as a single antimicrobial agent in coating for IRI prophylaxis. PMID:27806071

  18. Gentamicin concentration gradients in scala tympani perilymph following systemic applications

    PubMed Central

    Hahn, Hartmut; Salt, Alec N.; Schumacher, Ulrike; Plontke, Stefan K.

    2013-01-01

    In prior studies it was shown that round window membrane (RWM) application of gentamicin produced a robust baso-apical concentration gradient in the perilymph of scala tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intratympanic gentamicin applications for the treatment of Meniere’s disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications. Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg/bw over a period of three hours or as a 300 mg/kg/bw subcutaneous bolus injection. Three and five hours after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively. Ten sequential 1 μL-perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay. In contrast to local RWM delivery, systemic application of gentamicin resulted in highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with amount of drug applied and time before sampling. While the basal-apical gradient measured after local drug applications to the RW niche is likely the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of scala tympani relative to endolymph in the apical turns. PMID:24192668

  19. Gentamicin concentration gradients in scala tympani perilymph following systemic applications.

    PubMed

    Hahn, Hartmut; Salt, Alec N; Schumacher, Ulrike; Plontke, Stefan K

    2013-01-01

    It has been shown in prior studies that round window membrane (RWM) application of gentamicin produced a robust basal-apical concentration gradient in the perilymph of scala tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intratympanic gentamicin applications for the treatment of Ménière's disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications. Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg body weight (BW) over a period of 3 h or as a 300 mg/kg BW subcutaneous bolus injection. At 3 and 5 h after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively, and 10 sequential 1-µl perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay. In contrast to local RWM delivery, systemic application of gentamicin resulted in the highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with the amount of drug applied and time before sampling. While it is likely that the basal-apical gradient measured after local drug applications to the round window niche is the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from the blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of ST relative to endolymph in the apical turns. © 2013 S. Karger AG, Basel.

  20. Astaxanthin; a Promising Protector Against Gentamicin-Induced Nephrotoxicity in Rats.

    PubMed

    Mosaad, Yasser O; Gobba, Naglaa Abd El Khalik; Hussein, Mohammed A

    Gentamicin is an aminoglycoside antibiotic widely used against infections caused by Gram-negative microorganisms. Nephrotoxicity is the main limitation to its therapeutic use. The objective of this study was to evaluate the potential protective effect of astaxanthin on the renal damage generated by gentamicin in rats, in an attempt to understand its mechanism of action, which may pave the way for possible therapeutic applications. The daily oral administration of the astaxanthin at a concentration of 50 mg/kg for 15 days to gentamicin (80 mg/kg.b.w) treated rats showed a significant decrease (p<0.05) in plasma creatinine, urea, TNF-α as well as plasma and renal MDA and HP. The treatment also resulted in a significant increase in hemoglobin, plasma sodium, potassium and TAS as well as renal total protein, GSH, Pr-SHs, G6PD, SOD, GPx, CAT and GR levels. The histological examinations of renal tissues in this study revealed damage and glomerular infiltration in gentamicin treated rats. The presented data suggest that astaxanthin has a significant prophylactic action against gentamicin-induced nephrotoxicity in rats. The effect was more pronounced in case of astaxanthin pre-treatment compared with administration of astaxanthin post-treatment. Taken together, astaxanthin has a potential as a protective and therapeutic agent for nephrotoxicity and deserves clinical trial in the near future as an adjuvant therapy in patients treated with gentamicin.

  1. Gentamicin alters Akt-expression and its activation in the guinea pig cochlea.

    PubMed

    Heinrich, U-R; Strieth, S; Schmidtmann, I; Li, H; Helling, K

    2015-12-17

    Gentamicin treatment induces hair cell death or survival in the inner ear. Besides the well-known toxic effects, the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway was found to be involved in cell protection. After gentamicin application, the spatiotemporal expression patterns of Akt and its activated form (p-Akt) were determined in male guinea pigs. A single dose of 0.1 mL gentamicin (4 mg/ear/animal) was intratympanically injected. The auditory brainstem responses (ABRs) were recorded prior to application and 1, 2 and 7 days afterward. At these three time points the cochleae (n=10 in each case) were removed, transferred to fixative and embedded in paraffin. Seven ears were used as untreated controls. Gentamicin, Akt and p-Akt were identified immunohistochemically in various regions of the cochlea and their staining intensities were quantified on sections using digital image analysis. The application of gentamicin resulted in hearing loss with a concomitant up-regulation of Akt-expression in the organ of Corti and spiral ganglion cells and an additional activation in spiral ganglion cells. At the level of individual ears, clear intracellular correlations were found between Akt- and p-Akt-expression in the stria vascularis and interdental cells and, to a minor extent, in the spiral ligament and the organ of Corti. Furthermore, statistical evidence for the connection between gentamicin up-take and hearing loss was detected. The increase in Akt- and p-Akt-expression in the organ of Corti and spiral ganglion cells indicates a selected response of the cochlea against gentamicin toxicity. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Extracellular gentamicin reduces the activity of connexin hemichannels and interferes with purinergic Ca2+ signaling in HeLa cells

    PubMed Central

    Figueroa, Vania A.; Retamal, Mauricio A.; Cea, Luis A.; Salas, José D.; Vargas, Aníbal A.; Verdugo, Christian A.; Jara, Oscar; Martínez, Agustín D.; Sáez, Juan C.

    2014-01-01

    Gap junction channels (GJCs) and hemichannels (HCs) are composed of protein subunits termed connexins (Cxs) and are permeable to ions and small molecules. In most organs, GJCs communicate the cytoplasm of adjacent cells, while HCs communicate the intra and extracellular compartments. In this way, both channel types coordinate physiological responses of cell communities. Cx mutations explain several genetic diseases, including about 50% of autosomal recessive non-syndromic hearing loss. However, the possible involvement of Cxs in the etiology of acquired hearing loss remains virtually unknown. Factors that induce post-lingual hearing loss are diverse, exposure to gentamicin an aminoglycoside antibiotic, being the most common. Gentamicin has been proposed to block GJCs, but its effect on HCs remains unknown. In this work, the effect of gentamicin on the functional state of HCs was studied and its effect on GJCs was reevaluated in HeLa cells stably transfected with Cxs. We focused on Cx26 because it is the main Cx expressed in the cochlea of mammals where it participates in purinergic signaling pathways. We found that gentamicin applied extracellularly reduces the activity of HCs, while dye transfer across GJCs was not affected. HCs were also blocked by streptomycin, another aminoglycoside antibiotic. Gentamicin also reduced the adenosine triphosphate release and the HC-dependent oscillations of cytosolic free-Ca2+ signal. Moreover, gentamicin drastically reduced the Cx26 HC-mediated membrane currents in Xenopus laevis oocytes. Therefore, the extracellular gentamicin-induced inhibition of Cx HCs may adversely affect autocrine and paracrine signaling, including the purinergic one, which might partially explain its ototoxic effects. PMID:25237294

  3. Susceptibility of Malassezia pachydermatis to aminoglycosides.

    PubMed

    Silva, Freddy Alejandro; Conde-Felipe, Magnolia; Rosario, Inmaculada; Ferrer, Otilia; Real, Fernando; Déniz, Soraya; Acosta, Félix; Padilla, Daniel; Acosta-Hernández, Begoña

    2017-12-01

    Previous studies have evaluated the action of gentamicin against Malassezia pachydermatis. The aim of this study was to evaluate in vitro susceptibility of M. pachydermatis to the aminoglycosides- gentamicin, tobramycin, netilmicin and framycetin. The minimum inhibitory concentration (MIC) of gentamicin was determined following methods M27-A3 microdilution and Etest ® . The Etest ® was used to determine the minimum inhibitory concentration (MIC) of the tobramycin and netilmicin. The Kirby-Bauer test was used to determine the antibiotic susceptibility to the framycetin. The MIC50 and MIC90 were 8.12 μg/mL and 32.5 μg/mL by microdilution method for gentamicin. The MIC50, determined by the Etest ® , was 8 μg/mL for gentamicin and netilmicin and 64 μg/mL for tobramycin. The MIC90 was 16 and 32 μg/mL for gentamicin and netilmicin respectively. The MIC90 was outside of the detectable limits for tobramycin. To framycetin, 28 strains (40%) of the 70 M. pachydermatis isolates tested showed a diameter of 22 mm, 22 strains (31.42%) showed a diameter of 20 mm, 16 strains showed a diameter of ≤ 18 mm, and only 5.71% of the isolates showed a diameter of ≥ 22 mm. This study provides evidence of high in vitro activity of the aminoglycosides-gentamicin, tobramycin, netilmicin and framycetin against M. pachydermatis. For gentamicin Etest ® showed similar values of MIC50 y MIC90 that the obtained by microdilution method. We considered Etest ® method could be a good method for these calculations with aminoglycosides. © 2017 Blackwell Verlag GmbH.

  4. Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats.

    PubMed

    Apaydin Yildirim, Betul; Kordali, Saban; Terim Kapakin, Kubra Asena; Yildirim, Fatih; Aktas Senocak, Esra; Altun, Serdar

    2017-06-01

    The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC. subsp. plicatum ethanol extract (HPE) against gentamicin-induced nephrotoxicity. Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material. They were formed into six groups containing 6 rats each and were allowed to adapt to laboratory conditions for 7 d. Group I: control, 5% DMSO intraperitoneal (i.p.); Group II: HPE 100 mg/(kg·d) i.p.; Group III: HPE 200 mg/(kg·d) i.p.; Group IV: gentamicin as 80 mg/(kg·d) i.p.; Group V: gentamicin as 80 mg/(kg·d) i.p.+HPE 100 mg/(kg·d) i.p.; and Group VI: gentamicin as 80 mg/(kg·d) i.p.+HPE 200 mg/(kg·d) i.p. for 8 d. Following treatment, serum, liver, and kidney tissues were used to assess blood urea nitrogen (BUN), creatinine, enzymatic and non-enzymatic antioxidants, and lipid peroxidation. Gentamicin significantly increased serum BUN, creatinin, and liver and kidney levels of malondialdehyde (MDA). It also decreased the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin, liver and kidney oxidant marker, and tubular necrosis as well as by an increase in antioxidant enzymes. It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats. As a result, these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.

  5. Plasmid-Mediated High-Level Gentamicin Resistance among Enteric Bacteria Isolated from Pet Turtles in Louisiana

    PubMed Central

    Díaz, María Alejandra; Cooper, Richard Kent; Cloeckaert, Axel; Siebeling, Ronald John

    2006-01-01

    The sale of small turtles is banned by the Food and Drug Administration from the U.S. market due to concerns about their excretion of Salmonella spp. To produce a safe pet for the export market, the Louisiana pet turtle industry uses gentamicin sulfate baths (1,000 μg/ml) to eradicate Salmonella spp. from turtle eggs. In 1999, we analyzed bacterial samples recovered from turtle farms and found that strains of Salmonella enterica subsp. arizonae and other bacteria, such as Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were resistant to high concentrations of gentamicin (>2,000 μg/ml) and to other aminoglycosides. The goal of this study was to identify the gene(s) which contributes to the high-level gentamicin resistance phenotype observed in bacteria from environmental samples with turtle farming activity, particularly the salmonellae, and to estimate the incidence of such genes in these bacteria. R plasmids from gentamicin-resistant strains were transferred by conjugation and transformation to naive Escherichia coli cells. Cloning and sequencing of the gentamicin resistance determinants on these plasmids revealed the presence of the aminoglycoside acetyltransferase genes aac(3)-IIa and aac(3)-VIa; the latter was present as a gene cassette of a class 1 integron. Multiplex PCR assays showed that every gentamicin-resistant isolate carried one of these acetyltransferase genes. Pulsed-field gel electrophoresis and restriction enzyme digestion analysis of R plasmids carrying these genes revealed different restriction profiles and sizes, indicating a dissemination of the gentamicin resistance genes through mobile molecular elements. The data presented highlight the need to develop an alternate method for the eradication of Salmonella spp. from turtle eggs. PMID:16391058

  6. Evaluation of the Protective Role of Glycine max Seed Extract (Soybean Oil) in Drug-Induced Nephrotoxicity in Experimental Rats.

    PubMed

    Ramasamy, Anand; Jothivel, Nandhakumar; Das, Saibal; Swapna, A; Albert, Alice Padmini; Barnwal, Preeti; Babu, Dinesh

    2017-09-28

    This study was conducted to evaluate the nephroprotective effect of Glycine max seed extract (soybean oil) against gentamicin- and rifampicin-induced nephrotoxicity in Sprague-Dawley rats and to compare its effects with those of vitamin E, which has well-established antioxidant and nephroprotective effects. Sixty male Sprague-Dawley rats (body weight 150-210 g) were divided into 10 groups. The first five groups were treated for 14 consecutive days with normal saline (5 ml/kg, by mouth [p.o.]); gentamicin (80 mg/kg intraperitoneally [i.p.]); gentamicin (80 mg/kg, i.p.) + vitamin E (250 mg/kg p.o.); gentamicin (80 mg/kg i.p.) + soybean oil (2.5 ml/kg p.o.); and gentamicin (80 mg/kg, i.p.) + soybean oil (5 ml/kg p.o.), respectively. For the next five groups, the same group allocation was done, but gentamicin was replaced with rifampicin (1 g/kg i.p.). Various biomarkers for nephrotoxicity in serum and urine were evaluated along with histopathological examination of kidneys. Analysis of variance (ANOVA) was done following Tukey's multiple comparison test; p < .05 was considered significant. Soybean oil in both doses significantly (p < .005) decreased serum blood urea nitrogen, creatinine, urea, uric acid and urine volume, kidney weight, urinary sodium, urinary potassium, and total protein and significantly (p < .005) increased serum total protein and urine creatinine in gentamicin- and rifampicin-treated animals, exhibiting nephroprotective effects. Soybean oil also showed strong antioxidant effects, causing significant (p < .005) increase in kidney homogenate catalases, glutathione peroxidase, and superoxide dismutase and significant (p < .005) decrease in lipid peroxidase in gentamicin- and rifampicin-treated animals. Soybean oil demonstrated good nephroprotective activity due to antioxidant effects.

  7. Effects of high-dose gentamicin sulfate on neuromuscular blockade in halothane-anesthetized horses.

    PubMed

    Hague, B A; Martinez, E A; Hartsfield, S M

    1997-11-01

    To evaluate effects of a single high dose of gentamicin on neuromuscular function in horses anesthetized with halothane. 6 healthy adult horses. Halothane-anesthetized horses were positioned in left lateral recumbency, and the right hind limb was immobilized in a reusable fiberglass cast fixed to a steel frame. The hoof was attached to a force transducer, and resting tension of 0.93 +/- 0.16 kg was maintained. A supramaximal train-of-four stimulus of 2 Hz for a duration of 0.25 millisecond was applied to the superficial peroneal nerve every 20 seconds by a square-wave stimulator. The force of the evoked digital extensor tension was recorded to determine first muscle twitch tension, compared with the baseline value (T1%) and the ratio of the force of the fourth twitch to the first twitch (T4/T1). Data were recorded at 5, 10, 15, 30, and 60 minutes after i.v. administration of vehicle or gentamicin (6 mg/kg of body weight). There was a significant (P = 0.04) treatment-time interaction for the effect of gentamicin on T1%; T1% associated with vehicle decreased from 100% to 92% during the 60- minute study period, but no decrease was associated with gentamicin. For T4/T1, there was no significant effect of treatment or time or treatment-time interaction between gentamicin and vehicle. Gentamicin did not cause a decrease in initial muscular strength, nor did it impair the muscles' ability to sustain strength. A single high dose of gentamicin does not cause significant neuromuscular blockade when administered alone to healthy horses anesthetized with halothane.

  8. Plasmid-mediated high-level gentamicin resistance among enteric bacteria isolated from pet turtles in Louisiana.

    PubMed

    Díaz, María Alejandra; Cooper, Richard Kent; Cloeckaert, Axel; Siebeling, Ronald John

    2006-01-01

    The sale of small turtles is banned by the Food and Drug Administration from the U.S. market due to concerns about their excretion of Salmonella spp. To produce a safe pet for the export market, the Louisiana pet turtle industry uses gentamicin sulfate baths (1,000 microg/ml) to eradicate Salmonella spp. from turtle eggs. In 1999, we analyzed bacterial samples recovered from turtle farms and found that strains of Salmonella enterica subsp. arizonae and other bacteria, such as Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were resistant to high concentrations of gentamicin (>2,000 microg/ml) and to other aminoglycosides. The goal of this study was to identify the gene(s) which contributes to the high-level gentamicin resistance phenotype observed in bacteria from environmental samples with turtle farming activity, particularly the salmonellae, and to estimate the incidence of such genes in these bacteria. R plasmids from gentamicin-resistant strains were transferred by conjugation and transformation to naive Escherichia coli cells. Cloning and sequencing of the gentamicin resistance determinants on these plasmids revealed the presence of the aminoglycoside acetyltransferase genes aac(3)-IIa and aac(3)-VIa; the latter was present as a gene cassette of a class 1 integron. Multiplex PCR assays showed that every gentamicin-resistant isolate carried one of these acetyltransferase genes. Pulsed-field gel electrophoresis and restriction enzyme digestion analysis of R plasmids carrying these genes revealed different restriction profiles and sizes, indicating a dissemination of the gentamicin resistance genes through mobile molecular elements. The data presented highlight the need to develop an alternate method for the eradication of Salmonella spp. from turtle eggs.

  9. [Sensitivity of clinical Proteus strains to antibiotics and their combinations].

    PubMed

    Sheina, E P; Arutcheva, A A

    1978-05-01

    In 1976 isolation of Proteus from wounds of patients with various purulent processes amounted to 14.5 per cent. Serotypes 0-10, 0-3 and H-3 predominated among the isolates. Sensitivity of 35 clinical strains of Proteus to 10 antibiotics, furagin and nevigramone was studied by the method of serial dilutions in liquid media. All the isolates were highly resistant to the antibiotics except gentamicin, furagin and nevigramone, the MIC of which for most of the strains was 3.12, 1.6-3.12 and 6.25-12.5 gamma/ml, respectively. The effect of 14 combinations of chemotherapeutics was also studied. The combinations of gentamicin with carbenicillin, gentamicin with ampicillin and monomycin with ampicillin proved to be most effective against the Proteus strains tested. The following combinations may be of practical value: monomycin + carbenicillin, kanamycin + ampicillin, kanamycin + carbenicillin, ampicillin + furagin, gentamicin + nevigramone. The combinations of carbenicillin with furagin and gentamicin with furagin were also rational.

  10. [Gentamicin: various pharmacotherapeutic aspects in comparison with other aminoglycosides].

    PubMed

    de Visser, N A; van Gogh, H; van Miert, A S

    1985-02-15

    Gentamicin may be used in the treatment of infection with gram-negative bacteria including Pseudomonas spp and Proteus spp. Resistance will only appear in suboptimal or too prolonged courses of treatment and usually is due to 'multi-step mutation'. This resistance may be prevented, among others, by combined treatment with gentamicin and an antibiotic of the beta lactam group. When gentamicin is used correctly, it will have few toxic side-effects. Thus, 3 mg/kg of body weight three times daily will usually be indicated to ensure an optimum therapeutic effect. Parenteral administration of gentamicin would only appear to be useful in cases of bacteraemia and/or bacterial infection of the kidney and/or urinary excretory ducts; in the last-named case, the dose given at one time may be reduced by fifty per cent. Local treatment, the most recent method of which consists in administration by I(ntra-)T(racheal) route, apparently offers more prospects.

  11. Clinically Significant Enhancement of Voriconazole Efficacy by Moxifloxacin and Gentamicin in Fungal Keratitis.

    PubMed

    Matoba, Alice Y; Divatia, Mukul K; Arguello, Robert A; Chevez-Barrios, Paty

    2018-05-01

    To report the effect of topical antibiotics moxifloxacin 0.3% and gentamicin 0.3% on the clinical efficacy of topical antifungal agent voriconazole 1% in cases of culture- or biopsy-proven fungal keratitis. Two cases of fungal keratitis in which the addition of topical moxifloxacin or moxifloxacin and gentamicin led to an improved clinical response to topical voriconazole were reviewed retrospectively. One patient with clinical resistance of his fungal keratitis to both topical voriconazole and natamycin had resolution of his keratitis with the addition of topical moxifloxacin and gentamicin to voriconazole. One patient who had a poor response to topical voriconazole had a dramatic response to the increase of the voriconazole regimen and addition of moxifloxacin. In a subset of patients with fungal keratitis, the addition of topical moxifloxacin 0.3% or moxifloxacin 0.3% and gentamicin 0.3% may enhance the therapeutic effect of topical voriconazole 1%.

  12. Electrostatic assembly of binary nanoparticle superlattices using protein cages

    NASA Astrophysics Data System (ADS)

    Kostiainen, Mauri A.; Hiekkataipale, Panu; Laiho, Ari; Lemieux, Vincent; Seitsonen, Jani; Ruokolainen, Janne; Ceci, Pierpaolo

    2013-01-01

    Binary nanoparticle superlattices are periodic nanostructures with lattice constants much shorter than the wavelength of light and could be used to prepare multifunctional metamaterials. Such superlattices are typically made from synthetic nanoparticles, and although biohybrid structures have been developed, incorporating biological building blocks into binary nanoparticle superlattices remains challenging. Protein-based nanocages provide a complex yet monodisperse and geometrically well-defined hollow cage that can be used to encapsulate different materials. Such protein cages have been used to program the self-assembly of encapsulated materials to form free-standing crystals and superlattices at interfaces or in solution. Here, we show that electrostatically patchy protein cages--cowpea chlorotic mottle virus and ferritin cages--can be used to direct the self-assembly of three-dimensional binary superlattices. The negatively charged cages can encapsulate RNA or superparamagnetic iron oxide nanoparticles, and the superlattices are formed through tunable electrostatic interactions with positively charged gold nanoparticles. Gold nanoparticles and viruses form an AB8fcc crystal structure that is not isostructural with any known atomic or molecular crystal structure and has previously been observed only with large colloidal polymer particles. Gold nanoparticles and empty or nanoparticle-loaded ferritin cages form an interpenetrating simple cubic AB structure (isostructural with CsCl). We also show that these magnetic assemblies provide contrast enhancement in magnetic resonance imaging.

  13. pH-induced vesicle-to-micelle transition in amphiphilic diblock copolymer: investigation by energy transfer between in situ formed polymer embedded gold nanoparticles and fluorescent dye.

    PubMed

    Maiti, Chiranjit; Banerjee, Rakesh; Maiti, Saikat; Dhara, Dibakar

    2015-01-01

    The ability to regulate the formation of nanostructures through self-assembly of amphiphilic block copolymers is of immense significance in the field of biology and medicine. In this work, a new block copolymer synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization technique from poly(ethylene glycol) monomethyl ether acrylate (PEGMA) and Boc-l-tryptophan acryloyloxyethyl ester (Boc-l-trp-HEA) was found to spontaneously form pH-responsive water-soluble nanostructures after removal of the Boc group. While polymer vesicles or polymerosomes were formed at physiological pH, the micelles were formed at acidic pH (< 5.2), and this facilitated a pH-induced reversible vesicle-to-micelle transition. Formation of these nanostructures was confirmed by different characterization techniques, viz. transmission electron microscopy, dynamic light scattering, and steady-state fluorescence measurements. Further, these vesicles were successfully utilized to reduce HAuCl4 and stabilize the resulting gold nanoparticles (AuNPs). These AuNPs, confined within the hydrophobic shell of the vesicles, could participate in energy transfer process with fluorescent dye molecules encapsulated in the core of the vesicles, thus forming a nanometal surface energy transfer (NSET) pair. Subsequently, following the efficiency of energy transfer between this pair, it was possible to monitor the process of transition from vesicles to micelles. Thus, in this work, we have successfully demonstrated that NSET can be used to follow the transition between nanostructures formed by amphiphilic block copolymers.

  14. Synergistic antibiofilm efficacy of a gallotannin 1,2,6-tri-O-galloyl-β-D-glucopyranose from Terminalia chebula fruit in combination with gentamicin and trimethoprim against multidrug resistant uropathogenic Escherichia coli biofilms

    PubMed Central

    Chattopadhyay, Rabi Ranjan

    2017-01-01

    In recent years the emergence of multiple drug resistance microbes has become a global public health problem. The aim of the present investigation was to evaluate possible antibiofilm efficacy of a gallotannin 1,2,6-tri-O-galloyl-β-D-glucopyranose from Terminalia chebula fruits alone and in combination with gentamicin and trimethoprim against preformed biofilms of multidrug-resistant (MDR) uropathogenic E. coli isolates using microbroth dilution, checkerboard titration and kill kinetics methods. Test gallotannin showed > 50% antibiofilm efficacy after 24 h when administered alone whereas gentamicin and trimethoprim failed to do so. But in combination, test gallotannin/gentamicin and test gallotannin/trimethoprim showed 71.24±6.75% and 93.4±8.46% antibiofilm activity respectively. On the basis of FICI values, test gallotannin/gentamicin showed synergistic interactions against 71.42% and test gallotannin/trimethoprim against 85.71% biofilm forming test bacterial isolates. Kill-kinetics study confirmed their synergistic interactions. Thus, gentamicin and trimethoprim in combination with test gallotannin may have potential for treatment of urinary tract infections caused by biofilm forming MDR uropathogenic E. coli. PMID:28562631

  15. Treatment of peripheral vestibular dysfunction using photobiomodulation

    NASA Astrophysics Data System (ADS)

    Lee, Min Young; Hyun, Jai-Hwan; Suh, Myung-Whan; Ahn, Jin-Chul; Chung, Phil-Sang; Jung, Jae Yun; Rhee, Chung Ku

    2017-08-01

    Gentamicin, which is still used in modern medicine, is a known vestibular toxic agent, and various degrees of balance problems have been observed after exposure to this pharmacologic agent. Photobiomodulation is a candidate therapy for vertigo due to its ability to reach deep inner ear organs such as the cochlea. Previous reports have suggested that photobiomodulation can improve hearing and cochlea function. However, few studies have examined the effect of photobiomodulation on balance dysfunction. We used a rat model to mimic human vestibulopathy resulting from gentamicin treatment and evaluated the effect of photobiomodulation on vestibular toxicity. Slow harmonic acceleration (SHA) rotating platform testing was used for functional evaluation and both qualitative and quantitative epifluorescence analyses of cupula histopathology were performed. Animals were divided into gentamicin only and gentamicin plus laser treatment groups. Laser treatment was applied to one ear, and function and histopathology were evaluated in both ears. Decreased function was observed in both ears after gentamicin treatment, demonstrated by low gain and no SHA asymmetry. Laser treatment minimized the damage resulting from gentamicin treatment as shown by SHA asymmetry and recovered gain in the treated ear. Histology results reflected the functional results, showing increased hair cell density and epifluorescence intensity in laser-treated cupulae.

  16. Carbamazepine-loaded solid lipid nanoparticles and nanostructured lipid carriers: Physicochemical characterization and in vitro/in vivo evaluation.

    PubMed

    Scioli Montoto, S; Sbaraglini, M L; Talevi, A; Couyoupetrou, M; Di Ianni, M; Pesce, G O; Alvarez, V A; Bruno-Blanch, L E; Castro, G R; Ruiz, M E; Islan, G A

    2018-07-01

    Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternatives for drug delivery to the central nervous system. In the present work, four different nanoformulations of the antiepileptic drug Carbamazepine (CBZ) were designed and prepared by the homogenization/ultrasonication method, with encapsulation efficiencies ranging from 82.8 to 93.8%. The formulations remained stable at 4 °C for at least 3 months. Physicochemical and microscopic characterization were performed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), atomic force microscopy (AFM); thermal properties by differential scanning calorimetry (DSC), thermogravimetry (TGA) and X-ray diffraction analysis (XRD). The results indicated the presence of spherical shape nanoparticles with a mean particle diameter around 160 nm in a narrow size distribution; the entrapped CBZ displayed an amorphous state. The in vitro release profile of CBZ fitted into a Baker-Lonsdale model for spherical matrices and almost the 100% of the encapsulated drug was released in a controlled manner during the first 24 h. The apparent permeability of CBZ-loaded nanoparticles through a cell monolayer model was similar to that of the free drug. In vivo experiments in a mice model of seizure suggested protection by CBZ-NLC against seizures for at least 2 h after intraperitoneal administration. The developed CBZ-loaded lipid nanocarriers displayed optimal characteristics of size, shape and drug release and possibly represent a promising tool to improve the treatment of refractory epilepsy linked to efflux transporters upregulation. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Stability of hepatoprotecting agent IFC-305 encapsulated into sol-gel titania nanoparticles and drug release evaluation: water and drug concentration effect.

    PubMed

    Albarran, L; López, T; Quintana, P; Chagoya, V

    2012-03-01

    IFC-305 was encapsulated into nanostructured titania and functionalized with OH groups by the sol-gel process using titanium n-butoxide, to be used in a drug delivery system for the treatment of liver cancer. Synthesis was carried out at different molar hydrolysis ratios: 4, 8, 16 and 24 mol of water; and drug concentration of 10, 20 and 30%. Characterization of IFC-titania reservoirs was carried out by Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermal analysis (DTA-TGA), scanning electron microscopy (SEM), and N2 adsorption-desorption isotherms (BET), confirms that IFC-305 is entrapped and stabilized in the TiO2-OH matrix. Drug liberation in vitro was determined by UV spectrometry over a period of 1000 h. This study demonstrated that the higher water content and the higher amount of loaded IFC, favored hydrogen bonding between titania-OH surface and IFC-NH groups, increasing the rate of drug release.

  18. Plasmon-induced optical switching of electrical conductivity in porous anodic aluminum oxide films encapsulated with silver nanoparticle arrays.

    PubMed

    Huang, Chen-Han; Lin, Hsing-Ying; Lau, Ben-Chao; Liu, Chih-Yi; Chui, Hsiang-Chen; Tzeng, Yonhua

    2010-12-20

    We report on plasmon induced optical switching of electrical conductivity in two-dimensional (2D) arrays of silver (Ag) nanoparticles encapsulated inside nanochannels of porous anodic aluminum oxide (AAO) films. The reversible switching of photoconductivity greatly enhanced by an array of closely spaced Ag nanoparticles which are isolated from each other and from the ambient by thin aluminum oxide barrier layers are attributed to the improved electron transport due to the localized surface plasmon resonance and coupling among Ag nanoparticles. The photoconductivity is proportional to the power, and strongly dependent on the wavelength of light illumination. With Ag nanoparticles being isolated from the ambient environments by a thin layer of aluminum oxide barrier layer of controlled thickness in nanometers to tens of nanometers, deterioration of silver nanoparticles caused by environments is minimized. The electrochemically fabricated nanostructured Ag/AAO is inexpensive and promising for applications to integrated plasmonic circuits and sensors.

  19. PLA-PEG-PLA copolymer-based polymersomes as nanocarriers for delivery of hydrophilic and hydrophobic drugs: preparation and evaluation with atorvastatin and lisinopril.

    PubMed

    Danafar, H; Rostamizadeh, K; Davaran, S; Hamidi, M

    2014-10-01

    Tri-block poly(lactide)-poly(ethylene glycol)-poly(lactide) (PLA-PEG-PLA) copolymers were synthesized and used to prepare polymersomes loaded separately by the hydrophobic and hydrophilic model drugs, atorvastatin and lisinopril, respectively. The resulting nanostructures were characterized by various techniques such as FTIR, DSC, PCS and AFM. The polymersomes exhibited high encapsulation efficiencies of almost 78% and 70.8% for atorvastatin and lisinopril, respectively. Investigation on FTIR and DSC results revealed that such a high encapsulation efficiency is due to strong interaction between atorvastatin and the copolymer. The impact of drug/copolymer ratio and copolymer composition on drug-loading efficiency and drug release behavior were also studied. The results showed that in case of lisinopril, polymersomes exhibited a triphasic drug release, while for atorvastatin a biphasic release profile was obtained. Overall, the results indicated that PLA-PEG-PLA polymersomes can be considered as a promising carrier for both hydrophilic and hydrophobic drugs.

  20. Tuning the conductance of H2O@C60 by position of the encapsulated H2O

    PubMed Central

    Zhu, Chengbo; Wang, Xiaolin

    2015-01-01

    The change of conductance of single-molecule junction in response to various external stimuli is the fundamental mechanism for the single-molecule electronic devices with multiple functionalities. We propose the concept that the conductance of molecular systems can be tuned from inside. The conductance is varied in C60 with encapsulated H2O, H2O@C60. The transport properties of the H2O@C60-based nanostructure sandwiched between electrodes are studied using first-principles calculations combined with the non-equilibrium Green’s function formalism. Our results show that the conductance of the H2O@C60 is sensitive to the position of the H2O and its dipole direction inside the cage with changes in conductance up to 20%. Our study paves a way for the H2O@C60 molecule to be a new platform for novel molecule-based electronics and sensors. PMID:26643873

  1. Graphene-Encapsulated Nanosheet-Assembled Zinc-Nickel-Cobalt Oxide Microspheres for Enhanced Lithium Storage.

    PubMed

    Zhang, Qiaobao; Chen, Huixin; Han, Xiang; Cai, Junjie; Yang, Yong; Liu, Meilin; Zhang, Kaili

    2016-01-01

    The appropriate combination of hierarchical transition-metal oxide (TMO) micro-/nanostructures constructed from porous nanobuilding blocks with graphene sheets (GNS) in a core/shell geometry is highly desirable for high-performance lithium-ion batteries (LIBs). A facile and scalable process for the fabrication of 3D hierarchical porous zinc-nickel-cobalt oxide (ZNCO) microspheres constructed from porous ultrathin nanosheets encapsulated by GNS to form a core/shell geometry is reported for improved electrochemical performance of the TMOs as an anode in LIBs. By virtue of their intriguing structural features, the produced ZNCO/GNS core/shell hybrids exhibit an outstanding reversible capacity of 1015 mA h g(-1) at 0.1 C after 50 cycles. Even at a high rate of 1 C, a stable capacity as high as 420 mA h g(-1) could be maintained after 900 cycles, which suggested their great potential as efficient electrodes for high-performance LIBs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Is gentamicin necessary in the antimicrobial treatment for group B streptococcal infections in the elderly? An in vitro study with human blood products.

    PubMed

    Ruppen, Corinne; Decosterd, Laurent; Sendi, Parham

    2017-03-01

    According to expert opinions, gentamicin should be administered as an adjunct to penicillin against severe group B streptococcal (GBS) infections. Whether the adjunct is important is of particular interest for elderly patients. Not only is the risk of aminoglycoside nephrotoxicity higher in elderly persons, but their immune defence to bacterial infections may also be impaired. Time-kill assays with human blood products, such as serum, neutrophilic granulocytes (opsonophagocytic assays) and whole blood from healthy, elderly volunteers were performed to evaluate the effect of gentamicin in combination with penicillin. In time-kill assays with human serum and in opsonophagocytic assays, we saw a trend for faster killing with the penicillin-gentamicin combination therapy. This effect was seen 4 and 6 h after antibiotic exposure but not at time points evaluated at ≥8 h. In whole blood killing assays, no difference in killing rates was observed with adjunctive gentamicin therapy. The criteria for synergism were not fulfilled when the effect of penicillin-gentamicin combinations was compared with that of penicillin monotherapy. Rapid killing of GBS within the first few hours was observed in time-kill assays with human blood products. Considering that elderly people are prone to gentamicin nephrotoxicity and that in severe GBS infection a high penicillin dose is administered every 4-6 h, the prolonged use of adjunctive aminoglycosides in these infections requires caution.

  3. Measurement of plasma gentamicin concentrations postchemical ciliary body ablation in dogs with chronic glaucoma.

    PubMed

    Rankin, Amy J; Lanuza, Rick; KuKanich, Butch; Crumley, William C; Pucket, Jonathan D; Allbaugh, Rachel A; Meekins, Jessica M

    2016-01-01

    To investigate the absorption of gentamicin into the plasma after an intravitreal injection in dogs and to report the success rate of this procedure in lowering the intraocular pressure. Twenty-four client-owned dogs with chronic, end-stage glaucoma. Dogs received a unilateral (22) or bilateral (2) intravitreal injection of 25-40 mg of gentamicin (mean ± SD dose 2.57 ± 1.65 mg/kg and range 0.61-7.50 mg/kg) and 1 mg of dexamethasone per eye. Blood samples were collected at various time points following the intravitreal injection. Plasma concentrations of gentamicin were determined by liquid chromatography and mass spectrometry. The total plasma concentration of gentamicin ranged from 0.21 to 9.71 μg/mL (mean ± SD 2.15 ± 2.03). The mean gentamicin CMAX was 2.29 μg/mL at 2.54 h with a terminal half-life of 9.8 h. The success rate of the chemical ablation procedure was 86.4% (19/22 eyes) in dogs that had at least 1 month of follow-up. Intravitreal injection of gentamicin in eyes with chronic glaucoma resulted in detectable plasma levels in dogs and was successful in lowering the intraocular pressure in 86.4% of the eyes after the first procedure. © 2015 American College of Veterinary Ophthalmologists.

  4. Effect of pulsed ultrasound in combination with gentamicin on bacterial killing of biofilms on bone cements in vivo

    PubMed Central

    Ensing, G.T.; Roeder, B.L.; Nelson, J.L.; van Horn, J.R.; van der Mei, H.C.; Busscher, H.J.; Pitt, W.G.

    2008-01-01

    Aim The aim of this study is to investigate whether pulsed ultrasound in combination with gentamicin yields increased killing of bacterial biofilms on bone cements in vivo. Methods and Results Bacterial survival on bone cement in the presence and absence of ultrasound was compared in a rabbit model. Two bone cement samples with E. coli ATCC 10798 biofilm were implanted in a total of nine rabbits. In two groups bone cement disks loaded with gentamicin were used, and in one group unloaded bone cement disks in combination with systemically administered gentamicin were used. Pulsed ultrasound with a mean acoustic intensity of 167 mW cm−2 and a maximum acoustic intensity of 500 mW cm−2 was applied from 24 h till 72 h post surgery on one of the two implanted disks. After euthanization, the bacteria removed from the disk were quantified. Application of ultrasound, combined with gentamicin, reduced the biofilm in all three groups varying between 58 to 69% compared to the negative control. Ultrasound proved to be safe with respect to creating skin lesions. Conclusions Ultrasound resulted in an tendency of improved efficacy of gentamicin, either applied locally or systemically. Significance and impact of Study This study implies that ultrasound could improve the prevention of infection, especially because the biomaterials, gentamicin and ultrasound used in this model are all in clinical usage, but not yet combined in clinical practice. PMID:16108785

  5. Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania.

    PubMed

    Mwengee, William; Butler, Thomas; Mgema, Samuel; Mhina, George; Almasi, Yusuf; Bradley, Charles; Formanik, James B; Rochester, C George

    2006-03-01

    Over the past 50 years, antibiotics of choice for treatment of plague, including streptomycin, chloramphenicol, and tetracycline, have mostly become outdated or unavailable. To test gentamicin in the treatment of naturally occurring plague and the implications of its use in the treatment of bioterrorist plague, a randomized, comparative, open-label, clinical trial comparing monotherapy with gentamicin or doxycycline was conducted in Tanzania. Sixty-five adults and children with symptoms of bubonic, septicemic, or pneumonic plague of < or =3 days duration were enrolled in the study. Bubo aspirates and blood were cultured for Yersinia pestis. Acute-phase and convalescent-phase serum samples were tested for antibody against fraction 1 antigen of Y. pestis. Thirty-five patients were randomized to receive gentamicin (2.5 mg/kg intramuscularly every 12 h for 7 days), and 30 patients were randomized to receive doxycycline (100 mg [adults] and 2.2 mg/kg [children] orally every 12 h for 7 days). Serum creatinine concentrations were measured before and after treatment, and peak and trough concentrations of antibiotics were measured. Three patients, 2 of whom were treated with gentamicin and 1 of whom was treated with doxycycline, died on the first or second day of treatment, and these deaths were attributed to advanced disease and complications including pneumonia, septicemia, hemorrhage, and renal failure at the start of therapy. All other patients experienced cure or an improved condition after receiving therapy, resulting in favorable response rates of 94% for gentamicin (95% CI, 81.1%-99.0%) and 97% for doxycycline (95% CI, 83.4%-99.8%). Y. pestis isolates obtained from 30 patients belonged to biotype antigua and were susceptible to gentamicin and doxycycline, which had MICs of 0.13 mg/L and 0.25-0.5 mg/L, respectively. Serum concentrations of antibiotics were within therapeutic ranges, and adverse events were infrequent. Patients treated with gentamicin demonstrated a modest increase in the mean serum creatinine concentration after treatment (P<.05, by paired t test). Both gentamicin and doxycycline were effective therapies for adult and pediatric plague, with high rates of favorable responses and low rates of adverse events.

  6. Femtosecond laser modification of an array of vertically aligned carbon nanotubes intercalated with Fe phase nanoparticles

    PubMed Central

    2013-01-01

    Femtosecond lasers (FSL) are playing an increasingly important role in materials research, characterization, and modification. Due to an extremely short pulse width, interactions of FSL irradiation with solid surfaces attract special interest, and a number of unusual phenomena resulted in the formation of new materials are expected. Here, we report on a new nanostructure observed after the interaction of FSL irradiation with arrays of vertically aligned carbon nanotubes (CNTs) intercalated with iron phase catalyst nanoparticles. It was revealed that the FSL laser ablation transforms the topmost layer of CNT array into iron phase nanospheres (40 to 680 nm in diameter) located at the tip of the CNT bundles of conical shape. Besides, the smaller nanospheres (10 to 30 nm in diameter) are found to be beaded at the sides of these bundles. Some of the larger nanospheres are encapsulated into carbon shells, which sometime are found to contain CNTs. The mechanism of creation of such nanostructures is proposed. PMID:24004518

  7. Femtosecond laser modification of an array of vertically aligned carbon nanotubes intercalated with Fe phase nanoparticles.

    PubMed

    Labunov, Vladimir; Prudnikava, Alena; Bushuk, Serguei; Filatov, Serguei; Shulitski, Boris; Tay, Beng Kang; Shaman, Yury; Basaev, Alexander

    2013-09-03

    Femtosecond lasers (FSL) are playing an increasingly important role in materials research, characterization, and modification. Due to an extremely short pulse width, interactions of FSL irradiation with solid surfaces attract special interest, and a number of unusual phenomena resulted in the formation of new materials are expected. Here, we report on a new nanostructure observed after the interaction of FSL irradiation with arrays of vertically aligned carbon nanotubes (CNTs) intercalated with iron phase catalyst nanoparticles. It was revealed that the FSL laser ablation transforms the topmost layer of CNT array into iron phase nanospheres (40 to 680 nm in diameter) located at the tip of the CNT bundles of conical shape. Besides, the smaller nanospheres (10 to 30 nm in diameter) are found to be beaded at the sides of these bundles. Some of the larger nanospheres are encapsulated into carbon shells, which sometime are found to contain CNTs. The mechanism of creation of such nanostructures is proposed.

  8. Nano-structured silica coated mesoporous carbon micro-granules for potential application in water filtration

    NASA Astrophysics Data System (ADS)

    Das, Avik; Sen, D.; Mazumder, S.; Ghosh, A. K.

    2017-05-01

    A novel nano-composite spherical micro-granule has been synthesized using a facile technique of solvent evaporation induced assembly of nanoparticles for potential application in water filtration. The spherical micro-granule is comprised of nano-structured shell of hydrophilic silica encapsulating a hydrophobic mesoporous carbon at the core. Hierarchical structure of such core-shell micro-granules has been rigorously characterized using small-angle neutron and X-ray scattering techniques and complemented with scanning electron microscopy. The hydrophilic silica envelope around the carbon core helps in incorporation of such granules into the hydrophilic polymeric ultra-filtration membrane. The interstitial micro-pores present in the silica shell can serve as water transport channels and the mesoporus carbon core enhances the separation performance due its well adsorption characteristics. It has been found that the incorporation of such granules inside the ultra-filtration membrane indeed enhances the water permeability as well as the separation performance in a significant way.

  9. Transition metal ions mediated tyrosine based short peptide amphiphile nanostructures inhibit bacterial growth.

    PubMed

    Joshi, Khashti Ballabh; Singh, Ramesh; Mishra, Narendra Kumar; Kumar, Vikas; Vinayak, Vandana

    2018-05-17

    We report the design and synthesis of biocompatible small peptide based molecule for the controlled and targeted delivery of the encapsulated bioactive metal ions via transforming their internal nanostructures. Tyrosine based short peptide amphiphile (sPA) was synthesized which self-assembled into β-sheet like secondary structures. The self assembly of the designed sPA was modulated by using different bioactive transition metal ions which is confirmed by spectroscopic and microscopic techniques. These bioactive metal ions conjugated sPA hybrid structures are further used to develop antibacterial materials. It is due to the excellent antibacterial activity of zinc ions that the growth of clinically relevant bacteria such as E. Coli was inhibited in the presence of zinc-sPA conjugate. The bacterial test demonstrated that owing to high biocompatibility with bacterial cell, the designed sPA worked as metal ions delivery agent and therefore it can show great potential in locally addressing bacterial infections. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Lipids-based nanostructured lipid carriers (NLCs) for improved oral bioavailability of sirolimus.

    PubMed

    Yu, Qin; Hu, Xiongwei; Ma, Yuhua; Xie, Yunchang; Lu, Yi; Qi, Jianping; Xiang, Li; Li, Fengqian; Wu, Wei

    2016-05-01

    The main purpose of this study was to improve the oral bioavailability of sirolimus (SRL), a poorly water-soluble immunosuppressant, by encapsulating into lipids-based nanostructured lipid carriers (NLCs). SRL-loaded NLCs (SRL-NLCs) were prepared by a high-pressure homogenization method with glycerol distearates (PRECIROL ATO-5) as the solid lipid, oleic acid as the liquid lipids, and Tween 80 as the emulsifier. The SRL-NLCs prepared under optimum conditions was spherical in shape with a mean particle size of about 108.3 nm and an entrapment efficiency of 99.81%. In vitro release of SRL-NLCs was very slow, about 2.15% at 12 h, while in vitro lipolysis test showed fast digestion of the NLCs within 1 h. Relative oral bioavailability of SRL-NLCs in Beagle dogs was 1.81-folds that of the commercial nanocrystalline sirolimus tablets Rapamune®. In conclusion, the NLCs show potential to improve the oral bioavailability of SRL.

  11. A novel diblock of copolymer of (monomethoxy poly [ethylene glycol]-oleate) with a small hydrophobic fraction to make stable micelles/polymersomes for curcumin delivery to cancer cells

    PubMed Central

    Erfani-Moghadam, Vahid; Nomani, Alireza; Zamani, Mina; Yazdani, Yaghoub; Najafi, Farhood; Sadeghizadeh, Majid

    2014-01-01

    Curcumin is a potent natural anticancer agent, but its effectiveness is limited by properties such as very low solubility, high rate of degradation, and low rate of absorption of its hydrophobic molecules in vivo. To date, various nanocarriers have been used to improve the bioavailability of this hydrophobic biomaterial. This study investigates the encapsulation of curcumin in a novel nanostructure of monomethoxy poly(ethylene glycol)-oleate (mPEG-OA) and its anticancer effect. Tests were done to determine the critical micelle concentration (CMC), encapsulation efficiency, drug-loading efficiency, and cytotoxicity (against U87MG brain carcinoma cells and HFSF-PI3 cells as normal human fibroblasts) of some nanodevice preparations. The results of fluorescence microscopy and cell-cycle analyses indicated that the in vitro bioavailability of the encapsulated curcumin was significantly greater than that of free curcumin. Cytotoxicity evaluations showed that half maximal inhibitory concentrations of free curcumin and curcumin-loaded mPEG-OA for the U87MG cancer cell line were 48 μM and 24 μM, respectively. The Annexin-V-FLUOS assay was used to quantify the apoptotic effect of the prepared nanostructures. Apoptosis induction was observed in a dose-dependent manner after curcumin-loaded mPEG-OA treatments. Two common self-assembling structures, micelles and polymersomes, were observed by atomic force microscopy and dynamic light scattering, and the abundance of each structure was dependent on the concentration of the diblock copolymer. The mPEG-OA micelles had a very low CMC (13.24 μM or 0.03 g/L). Moreover, atomic force microscopy and dynamic light scattering showed that the curcumin-loaded mPEG-OA polymersomes had very stable structures, and at concentrations 1,000 times less than the CMC, at which the micelles disappear, polymersomes were the dominant structures in the dispersion with a reduced size distribution below 150 nm. Overall, the results from these tests revealed that this nanocarrier can be considered as an appropriate drug delivery system for delivering curcumin to cancer cells. PMID:25489242

  12. Refilling of carbon nanotube cartridges for 3D nanomanufacturing

    NASA Astrophysics Data System (ADS)

    Bekarevich, Raman; Toyoda, Masami; Baba, Shuichi; Nakata, Toshihiko; Hirahara, Kaori

    2016-03-01

    Metal-filled carbon nanotubes (CNTs) are known to be used as pen-tip injectors for 3D manufacturing on the nanoscale. However, the CNT interior cannot accumulate enough material to fabricate complex metallic nanostructures. Therefore a method for refilling the CNT cartridge needs to be developed. The strategy for refilling of CNT cartridges is suggested in this study. Controlled growth of gold nanowires in the interior of isolated CNTs using a real-time manipulator installed in a transmission electron microscope is reported herein. The encapsulation process of discrete gold nanoparticles in the hollow spaces of open-ended multi-wall CNTs was evaluated in detail. The experimental results reveal that the serial loading of isolated gold nanoparticles allows the control of the length of the loaded nanowires with nanometer accuracy. Thermophoresis and the coalescence of gold nanoparticles are assumed to be the primary mechanisms responsible for gold loading into a CNT cartridge.Metal-filled carbon nanotubes (CNTs) are known to be used as pen-tip injectors for 3D manufacturing on the nanoscale. However, the CNT interior cannot accumulate enough material to fabricate complex metallic nanostructures. Therefore a method for refilling the CNT cartridge needs to be developed. The strategy for refilling of CNT cartridges is suggested in this study. Controlled growth of gold nanowires in the interior of isolated CNTs using a real-time manipulator installed in a transmission electron microscope is reported herein. The encapsulation process of discrete gold nanoparticles in the hollow spaces of open-ended multi-wall CNTs was evaluated in detail. The experimental results reveal that the serial loading of isolated gold nanoparticles allows the control of the length of the loaded nanowires with nanometer accuracy. Thermophoresis and the coalescence of gold nanoparticles are assumed to be the primary mechanisms responsible for gold loading into a CNT cartridge. Electronic supplementary information (ESI) available: Variations of loading of the initial nanoparticle into the CNT, movies demonstrating the processes of the loading of the initial nanoparticle and elongation of encapsulated nanowire. See DOI: 10.1039/c5nr08712k

  13. Mycobacteria inactivation using Engineered Water Nanostructures (EWNS).

    PubMed

    Pyrgiotakis, Georgios; McDevitt, James; Gao, Ya; Branco, Alan; Eleftheriadou, Mary; Lemos, Bernardo; Nardell, Edward; Demokritou, Philip

    2014-08-01

    Airborne transmitted pathogens such as Mycobacterium tuberculosis (Mtb) cause serious, often fatal infectious disease with enormous global health implications. Due to their unique cell wall and slow growth, mycobacteria are among the most resilient microbial forms. Herein we evaluate the ability of an emerging, chemical-free, nanotechnology-based method to inactivate M. parafortuitum (Mtb surrogate). This method is based on the transformation of atmospheric water vapor into engineered water nano-structures (EWNS) via electrospray. We demonstrate that the EWNS can interact with and inactivate airborne mycobacteria, reducing their concentration levels significantly. Additionally, EWNS can inactivate M. parafortuitum on surfaces eight times faster than the control. The mechanism of mycobacteria inactivation was also investigated in this study. It was demonstrated that the EWNS effectively deliver the reactive oxygen species, encapsulated during the electrospray process, to the bacteria oxidizing their cell membrane resulting into inactivation. Overall, this is a method with the potential to become an effective intervention technology in the battle against airborne infections. This study demonstrates the feasibility of mycobacterium inactivation in airborne form or on contact surfaces using electrospray activated water nano-structures. Given that the method is free of toxic chemicals, this might become an important tool in the prevention of mycobacterial infections, which are notoriously hard to treat. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Interfacing with Neural Activity via Femtosecond Laser Stimulation of Drug-Encapsulating Liposomal Nanostructures

    PubMed Central

    Mackay, Sean M.; Wui Tan, Eng

    2016-01-01

    External control over rapid and precise release of chemicals in the brain potentially provides a powerful interface with neural activity. Optical manipulation techniques, such as optogenetics and caged compounds, enable remote control of neural activity and behavior with fine spatiotemporal resolution. However, these methods are limited to chemicals that are naturally present in the brain or chemically suitable for caging. Here, we demonstrate the ability to interface with neural functioning via a wide range of neurochemicals released by stimulating loaded liposomal nanostructures with femtosecond lasers. Using a commercial two-photon microscope, we released inhibitory or excitatory neurochemicals to evoke subthreshold and suprathreshold changes in membrane potential in a live mouse brain slice. The responses were repeatable and could be controlled by adjusting laser stimulation characteristics. We also demonstrate the release of a wider range of chemicals—which previously were impossible to release by optogenetics or uncaging—including synthetic analogs of naturally occurring neurochemicals. In particular, we demonstrate the release of a synthetic receptor-specific agonist that exerts physiological effects on long-term synaptic plasticity. Further, we show that the loaded liposomal nanostructures remain functional for weeks in a live mouse. In conclusion, we demonstrate new techniques capable of interfacing with live neurons, and extendable to in vivo applications. PMID:27896311

  15. Scalable 2D Mesoporous Silicon Nanosheets for High-Performance Lithium-Ion Battery Anode.

    PubMed

    Chen, Song; Chen, Zhuo; Xu, Xingyan; Cao, Chuanbao; Xia, Min; Luo, Yunjun

    2018-03-01

    Constructing unique mesoporous 2D Si nanostructures to shorten the lithium-ion diffusion pathway, facilitate interfacial charge transfer, and enlarge the electrode-electrolyte interface offers exciting opportunities in future high-performance lithium-ion batteries. However, simultaneous realization of 2D and mesoporous structures for Si material is quite difficult due to its non-van der Waals structure. Here, the coexistence of both mesoporous and 2D ultrathin nanosheets in the Si anodes and considerably high surface area (381.6 m 2 g -1 ) are successfully achieved by a scalable and cost-efficient method. After being encapsulated with the homogeneous carbon layer, the Si/C nanocomposite anodes achieve outstanding reversible capacity, high cycle stability, and excellent rate capability. In particular, the reversible capacity reaches 1072.2 mA h g -1 at 4 A g -1 even after 500 cycles. The obvious enhancements can be attributed to the synergistic effect between the unique 2D mesoporous nanostructure and carbon capsulation. Furthermore, full-cell evaluations indicate that the unique Si/C nanostructures have a great potential in the next-generation lithium-ion battery. These findings not only greatly improve the electrochemical performances of Si anode, but also shine some light on designing the unique nanomaterials for various energy devices. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Icosahedral plant viral nanoparticles - bioinspired synthesis of nanomaterials/nanostructures.

    PubMed

    Narayanan, Kannan Badri; Han, Sung Soo

    2017-10-01

    Viral nanotechnology utilizes virus nanoparticles (VNPs) and virus-like nanoparticles (VLPs) of plant viruses as highly versatile platforms for materials synthesis and molecular entrapment that can be used in the nanotechnological fields, such as in next-generation nanoelectronics, nanocatalysis, biosensing and optics, and biomedical applications, such as for targeting, therapeutic delivery, and non-invasive in vivo imaging with high specificity and selectivity. In particular, plant virus capsids provide biotemplates for the production of novel nanostructured materials with organic/inorganic moieties incorporated in a very precise and controlled manner. Interestingly, capsid proteins of spherical plant viruses can self-assemble into well-organized icosahedral three-dimensional (3D) nanoscale multivalent architectures with high monodispersity and structural symmetry. Using viral genetic and protein engineering of icosahedral viruses with a variety of sizes, the interior, exterior and the interfaces between coat protein (CP) subunits can be manipulated to fabricate materials with a wide range of desirable properties allowing for biomineralization, encapsulation, infusion, controlled self-assembly, and multivalent ligand display of nanoparticles or molecules for varied applications. In this review, we discuss the various functional nanomaterials/nanostructures developed using the VNPs and VLPs of different icosahedral plant viruses and their nano(bio)technological and nanomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Production and characterization of nanostructured lipid carriers and solid lipid nanoparticles containing lycopene for food fortification.

    PubMed

    Akhoond Zardini, Ali; Mohebbi, Mohebbat; Farhoosh, Reza; Bolurian, Shadi

    2018-01-01

    In this study, lycopene, was loaded on nanostructured lipid carrier and solid lipid nanoparticles using combination of high shear homogenization and ultrasonication method. Effect of applied lipids types, nanocarrier's type and lycopene loading on physicochemical properties of developed nanocarriers were studied. Particle sizes of developed nanocarriers were between 74.93 and 183.40 nm. Encapsulation efficiency of nanostructured lipid carrier was significantly higher than solid lipid nanoparticles. Morphological study of developed nanocarriers using scanning electron microscopy showed spherical nanoparticles with smooth surface. Lycopene was entrapped in nanocarriers without any chemical interaction with coating material according to Fourier transform infrared spectroscopy spectrum and differential scanning calorimetry thermogram. Glycerol monostearate containing nanoparticles showed phase separation after 30 days in 6 and 25 °C, whereas this event was not observed in nanosuspensions that produced by glycerol distearate. Lycopene release in gastrointestinal condition was studied by the dialysis bag method. To evaluate nanocarrier's potential for food fortification, developed lycopene-loaded nanocarriers were added to orange drink. Results of sensory analysis indicated that nanoencapsulation could obviate the poor solubility and tomato after taste of lycopene. Fortified sample with lycopene nanocarriers didn't show significant difference with blank orange drink sample except in orange odor.

  18. Rational design and synthesis of yolk-shell ZnGa2O4@C nanostructure with enhanced lithium storage properties

    NASA Astrophysics Data System (ADS)

    Han, Nao; Xia, Yuguo; Han, Yanyang; Jiao, Xiuling; Chen, Dairong

    2018-03-01

    The ability to create hybrid nanostructure with synergistic effect and confined morphology to achieve high performance and long-term stability is high desirable in lithium ion batteries. Although transition metal oxides as anode material reveal high theoretical capacities, the significant volume changes during repeated lithium insertion and extraction cause pulverization of electrode materials, resulting in rapid fade in capacity. Herein, yolk-shell nanostructure of ZnGa2O4 encapsulated by amorphous carbon is rationally designed and synthesized through two-step surface coating followed by thermal treatment and etching process. It is noteworthy that ZnGa2O4@C with yolk-shell structure is superior to pristine ZnGa2O4 and ZnGa2O4@C with core-shell structure in term of lithium storage. The stable reversible capacity of yolk-shell ZnGa2O4@C can be retained at 657.2 mAh g-1 at current density of 1 A g-1 after completion of 300 cycles, which also reveals superior rate performance. The appropriate carbon shell and void space involved in the yolk-shell structure are considered to be the crucial factor in accommodating volume expansion as well as preserving the structural integrity of yolk-shell ZnGa2O4@C.

  19. Gentamicin tissue concentration in various avian species following recommended dosage therapy

    USGS Publications Warehouse

    Bush, M.; Locke, D.; Neal, L.A.; Carpenter, J.W.

    1981-01-01

    Plasma and tissue drug concentrations were compared in eastern bobwhite quail (Colinus virginianus virginianus) and pigeons (Columba livia) given gentamicin by IM administration at the dosage of 10 mg/kg, and in greater sandhill cranes (Grus canadensis tabida) and hybrid rosybill ducks (Netta sp) given the same antibiotic at a dosage of 5 mg/kg. Quail and cranes had significantly higher liver concentrations of gentamicin at 6 hours after injection than did pigeons and ducks. Cranes had significantly higher plasma concentrations than did ducks at 6 hours after injection. Compared with plasma values, gentamicin concentrations were significantly higher in the liver of cranes at 12 hours after injection, and in the kidneys at 18 hours.

  20. Self-assembling peptide amphiphile nanostructures for cancer therapy

    NASA Astrophysics Data System (ADS)

    Soukasene, Stephen

    The application of nanotechnology to cancer therapy shows great promise for reducing the burden of the disease. By virtue of their size, nanoscale objects preferentially accumulate in tumor tissue through an enhanced permeability and retention (EPR) effect. However, to fully overcome the issues that limit current cancer treatments, viable nanostructures must also impart multifunctionality and be fully compatible with their biological surrounds. The self-assembling peptide amphiphile (PA) materials studied extensively in the Stupp Research Group form very biocompatible high aspect ratio nanostructures that meet these criteria. This thesis investigates the development of PA nanostructures designed to treat cancer. We first look to use the PA as a drug delivery vehicle by entrapping a small hydrophobic anti-cancer drug, camptothecin, in the core of the nanostructures. Using a solvent evaporation technique to load the drug into the PA nanofibers, we are able to improve the aqueous solubility of the molecule by nearly 30-fold. TEM and AFM studies show that entrapment of drug molecules does not disrupt the self-assembled morphology of the nanofiber. In vitro and in vivo studies are also conducted to demonstrate the bioactivity of the drug after its entrapment. As a potential platform for novel therapeutics, we next develop techniques for using light irradiation to trigger self-assembly inside the confined space of liposomes. We encapsulate PA monomers that assemble under acidic conditions along with a photoacid generator inside liposomes. Upon exposure to 254 nm light, the PA monomers self assemble inside the liposome to form nanostructures, which we observe through a quick freeze/deep etch technique that allows us to look inside the liposomes by SEM and TEM. Last of all, the development and discovery of epitopes for targeting PA nanostructures to tumors are explored. Using phage display technology we generate two groups of peptide sequences, one of which can potentially target tumor blood vessel formation, while the other is directed toward the ErbB2 receptor, which is over-expressed in certain aggressive breast cancers. Two peptide sequences from the literature that target breast cancer are also incorporated into PA molecules and we assess their biological affinity in vitro and in vivo.

  1. Porous Hydroxyapatite Bioceramic Scaffolds for Drug Delivery and Bone Regeneration

    NASA Astrophysics Data System (ADS)

    Loca, Dagnija; Locs, Janis; Salma, Kristine; Gulbis, Juris; Salma, Ilze; Berzina-Cimdina, Liga

    2011-10-01

    The conventional methods of supplying a patient with pharmacologic active substances suffer from being very poorly selective, so that damage can occurs to the healthy tissues and organs, different from the intended target. In addition, high drug doses can be required to achieve the desired effect. An alternative approach is based on the use of implantable delivery tools, able to release the active substance in a controlled way. In the current research local drug delivery devices containing 8mg of gentamicin sulphate were prepared using custom developed vacuum impregnation technique. In vitro dissolution tests showed that gentamicin release was sustained for 12h. In order to decrease gentamicin release rate, biopolymer coatings were applied and coating structure investigated. The results showed that gentamicin release can be sustained for more than 70h for poly(epsilon-caprolactone) coated calcium phosphate scaffolds. From poly lactic acid and polyvinyl alcohol coated scaffolds gentamicin was released within 20h and 50h, respectively.

  2. Intestinal transport of gentamicin with a novel, glycosteroid drug transport agent

    NASA Technical Reports Server (NTRS)

    Axelrod, H. R.; Kim, J. S.; Longley, C. B.; Lipka, E.; Amidon, G. L.; Kakarla, R.; Hui, Y. W.; Weber, S. J.; Choe, S.; Sofia, M. J.

    1998-01-01

    PURPOSE: The objective was to investigate the ability of a glycosteroid (TC002) to increase the oral bioavailability of gentamicin. METHODS: Admixtures of gentamicin and TC002 were administered to the rat ileum by injection and to dogs by ileal or jejunal externalized ports, or PO. Bioavailability of gentamicin was determined by HPLC. 3H-TC002 was injected via externalized cannulas into rat ileum or jejunum, or PO and its distribution and elimination was determined. The metabolism of TC002 in rats was evaluated by solid phase extraction and HPLC analysis of plasma, urine and feces following oral or intestinal administration. RESULTS: The bioavailability of gentamicin was substantially increased in the presence of TC002 in both rats and dogs. The level of absorption was dependent on the concentration of TC002 and site of administration. Greatest absorption occurred following ileal orjejunal administration. TC002 was significantly more efficacious than sodium taurocholate, but similar in cytotoxicity. TC002 remained primarily in the GI tract following oral or intestinal administration and cleared rapidly from the body. It was only partly metabolized in the GI tract, but was rapidly and completely converted to its metabolite in plasma and urine. CONCLUSIONS: TC002 shows promise as a new drug transport agent for promoting intestinal absorption of polar molecules such as gentamicin.

  3. Sound damage and gentamicin treatment produce different patterns of damage to the efferent innervation of the chick cochlea.

    PubMed

    Ofsie, M S; Hennig, A K; Messana, E P; Cotanche, D A

    1997-11-01

    Both sound exposure and gentamicin treatment cause damage to sensory hair cells in the peripheral chick auditory organ, the basilar papilla. This induces a regeneration response which replaces hair cells and restores auditory function. Since functional recovery requires the re-establishment of connections between regenerated hair cells and the central nervous system, we have investigated the effects of sound damage and gentamicin treatment on the neuronal elements within the cochlea. Whole-mount preparations of basilar papillae were labeled with phalloidin to label the actin cytoskeleton and antibodies to neurofilaments, choline acetyltransferase, and synapsin to label neurons; and examined by confocal laser scanning microscopy. When chicks are treated with gentamicin or exposed to acoustic overstimulation, the transverse nerve fibers show no changes from normal cochleae assayed in parallel. Efferent nerve terminals, however, disappear from areas depleted of hair cells following acoustic trauma. In contrast, efferent nerve endings are still present in the areas of hair cell loss following gentamicin treatment, although their morphological appearance is greatly altered. These differences in the response of efferent nerve terminals to sound exposure versus gentamicin treatment may account, at least in part, for the discrepancies reported in the time of recovery of auditory function.

  4. In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites.

    PubMed

    Cui, Xu; Gu, Yifei; Li, Le; Wang, Hui; Xie, Zhongping; Luo, Shihua; Zhou, Nai; Huang, Wenhai; Rahaman, Mohamed N

    2013-10-01

    Borate bioactive glass-based composites have been attracting interest recently as an osteoconductive carrier material for local antibiotic delivery. In the present study, composites composed of borate bioactive glass particles bonded with a chitosan matrix were prepared and evaluated in vitro as a carrier for gentamicin sulfate. The bioactivity, degradation, drug release profile, and compressive strength of the composite carrier system were studied as a function of immersion time in phosphate-buffered saline at 37 °C. The cytocompatibility of the gentamicin sulfate-loaded composite carrier was evaluated using assays of cell proliferation and alkaline phosphatase activity of osteogenic MC3T3-E1 cells. Sustained release of gentamicin sulfate occurred over ~28 days in PBS, while the bioactive glass converted continuously to hydroxyapatite. The compressive strength of the composite loaded with gentamicin sulfate decreased from the as-fabricated value of 24 ± 3 MPa to ~8 MPa after immersion for 14 days in PBS. Extracts of the soluble ionic products of the borate glass/chitosan composites enhanced the proliferation and alkaline phosphatase activity of MC3T3-E1 cells. These results indicate that the gentamicin sulfate-loaded composite composed of chitosan-bonded borate bioactive glass particles could be useful clinically as an osteoconductive carrier material for treating bone infection.

  5. Discontinuation of peri-operative gentamicin use for indwelling urinary catheter manipulation in orthopaedic surgery.

    PubMed

    Bond, Stuart E; Boutlis, Craig S; Jansen, Stuart G; Miyakis, Spiros

    2017-11-01

    Gentamicin has historically been used prior to insertion and removal of indwelling urinary catheters (IDCs) around elective joint replacement surgery to prevent infection; however, this indication is not recognized in the Australian Therapeutic Guidelines: Antibiotic and the paradigm for safe use of gentamicin has shifted. The antimicrobial stewardship team of a 500 bed tertiary regional hospital performed a retrospective clinical study of gentamicin IDC prophylaxis around total hip and knee arthroplasties. Results were presented to the orthopaedic surgeons. A literature review identified no guidelines to support gentamicin prophylaxis and only a very low risk of bacteraemia associated with IDC insertion/removal in patients with established bacteriuria. Consensus was reached with the surgeons to discontinue this practice. Subsequent prospective data collection was commenced to determine effectiveness, with weekly feedback to the Department Head of Orthopaedics. Data from 137 operations pre-intervention (6 months) were compared with 205 operations post-intervention (12 months). The median patient age was 72 years in both groups. Following the intervention, reductions in gentamicin use were demonstrated for IDC insertion (59/137 (42%) to 4/205 (2%), P < 0.01) and removal (39/137 (28%) to 6/205 (3%), P < 0.01). No gentamicin use was observed during the final 40 weeks of the post-intervention period. There were no significant differences between the groups for pre-operative bacteriuria, surgical site infections or acute kidney injury. A collaborative approach using quality improvement methodology can lead to an evidence-based reappraisal of established practice. Regular rolling audits and timely feedback were useful in sustaining change. © 2016 Royal Australasian College of Surgeons.

  6. Effect of pulsed ultrasound in combination with gentamicin on bacterial viability in biofilms on bone cements in vivo.

    PubMed

    Ensing, G T; Roeder, B L; Nelson, J L; van Horn, J R; van der Mei, H C; Busscher, H J; Pitt, W G

    2005-01-01

    The aim of this study is to investigate whether pulsed ultrasound (US) in combination with gentamicin yields a decreased viability of bacteria in biofilms on bone cements in vivo. Bacterial survival on bone cement in the presence and absence of ultrasound was compared in a rabbit model. Two bone cement samples with an Escherichia coli ATCC 10798 biofilm were implanted in a total of nine rabbits. In two groups bone cement discs loaded with gentamicin, freshly prepared and aged were used, and in one group unloaded bone cement discs in combination with systemically administered gentamicin. Pulsed ultrasound with a frequency of 28.48 kHz and a maximum acoustic intensity of 500 mW cm(-2) was applied continuously from 24 h till 72 h postsurgery on one of the two implanted discs. After euthanization and removal of the bacteria from the discs, the number of viable bacteria were quantified and skin samples were analysed for histopathological examination. Application of ultrasound, combined with gentamicin, reduced the viability of the biofilms in all three groups varying between 58 and 69% compared with the negative control. Histopathological examinations showed no skin lesions. Ultrasound resulted in a tendency of improved efficacy of gentamicin, either applied locally or systemically. Usage of ultrasound in this model proved to be safe. This study implies that ultrasound could improve the prevention of infection immediately after surgery, especially because the biomaterials, gentamicin and ultrasound used in this model are all in clinical usage, but not yet combined in clinical practice.

  7. Standard dosing of amikacin and gentamicin in critically ill patients results in variable and subtherapeutic concentrations.

    PubMed

    Roger, Claire; Nucci, Bastian; Molinari, Nicolas; Bastide, Sophie; Saissi, Gilbert; Pradel, Gael; Barbar, Saber; Aubert, Clément; Lloret, Sophie; Elotmani, Loubna; Polge, Anne; Lefrant, Jean-Yves; Roberts, Jason A; Muller, Laurent

    2015-07-01

    Low peak plasma concentrations (Cmax) of amikacin and gentamicin are reported in intensive care unit (ICU) patients after administration of the first dose. The present study aimed to describe the proportion of ICU patients in whom an adequate Cmax was achieved throughout the course of therapy. Septic ICU patients with an indication for intravenous amikacin or gentamicin were eligible for inclusion in this single-centre observational study. The first and subsequent doses and the corresponding Cmax values were recorded. The target Cmax was ≥60mg/L for amikacin and ≥30mg/L for gentamicin. Amikacin and gentamicin plasma concentrations were available in 66 and 24 patients, respectively (59±17 years; 79±19kg; height 169±12cm; SAPS II score 46±19). Pulmonary, abdominal and urinary tract infections were diagnosed in 64 patients. Culture-positive infection was confirmed in 65 patients (72%). A target first Cmax was achieved in 17/90 patients (19%). For amikacin, the target Cmax was achieved in 16/66 patients (24%) after the initial dose. In the 50 remaining patients, a change in dosing was performed in 14 patients, leading adequate peak plasma level in 2 patients. For gentamicin, the targeted Cmax was achieved in only 1/24 patient (4%) after the initial dose and was never achieved after the third dose. In conclusion, standard dosing of amikacin or gentamicin led to adequate Cmax in only 19% of patients. Subtherapeutic Cmax were not significantly corrected after subsequent doses. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  8. Intraoperative intra-articular injection of gentamicin: will it decrease the risk of infection in total shoulder arthroplasty?

    PubMed

    Lovallo, Jeffrey; Helming, Jarrett; Jafari, S Mehdi; Owusu-Forfie, Afia; Donovan, Skye; Minnock, Christopher; Adib, Farshad

    2014-09-01

    Deep infection is a debilitating complication after shoulder arthroplasty. Intra-articular injection of antibiotic can give a higher concentration compared with intravenous administration. We hypothesized that a group of patients given an intra-articular, intraoperative injection of gentamicin would report a lower infection rate than a group without local antibiotics. Between 2005 and 2011, the senior author performed 507 shoulder arthroplasties. We retrospectively reviewed all of those cases. All patients were administered systemic prophylactic antibiotics. Beginning in June 2007, patients were also injected with 160 mg of gentamicin in the glenohumeral joint at the end of their surgery. Patient records were examined for preexisting medical conditions, type of surgery, and presence of infection. Patients receiving surgery before 2007 were compared with those after to determine the effect of prophylactic gentamicin administration in preventing deep infection associated with surgery. All patients were observed for a minimum of 1 year. Of the 507 surgeries, 164 were performed before 2007 (without intra-articular injection of gentamicin; group A) and 343 were performed with addition of gentamicin (group B). In group A, 5 patients presented with infection (3.0%) compared with 1 in group B (0.29%). The gender, mean age, mean body mass index, and prevalence of comorbidities were similar between the groups. The data from this study support the conclusion that intra-articular intraoperative gentamicin administration may reduce postoperative infection. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  9. Sodium-Glucose Transporter-2 (SGLT2; SLC5A2) Enhances Cellular Uptake of Aminoglycosides

    PubMed Central

    Jiang, Meiyan; Wang, Qi; Karasawa, Takatoshi; Koo, Ja-Won; Li, Hongzhe; Steyger, Peter S.

    2014-01-01

    Aminoglycoside antibiotics, like gentamicin, continue to be clinically essential worldwide to treat life-threatening bacterial infections. Yet, the ototoxic and nephrotoxic side-effects of these drugs remain serious complications. A major site of gentamicin uptake and toxicity resides within kidney proximal tubules that also heavily express electrogenic sodium-glucose transporter-2 (SGLT2; SLC5A2) in vivo. We hypothesized that SGLT2 traffics gentamicin, and promotes cellular toxicity. We confirmed in vitro expression of SGLT2 in proximal tubule-derived KPT2 cells, and absence in distal tubule-derived KDT3 cells. D-glucose competitively decreased the uptake of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), a fluorescent analog of glucose, and fluorescently-tagged gentamicin (GTTR) by KPT2 cells. Phlorizin, an SGLT2 antagonist, strongly inhibited uptake of 2-NBDG and GTTR by KPT2 cells in a dose- and time-dependent manner. GTTR uptake was elevated in KDT3 cells transfected with SGLT2 (compared to controls); and this enhanced uptake was attenuated by phlorizin. Knock-down of SGLT2 expression by siRNA reduced gentamicin-induced cytotoxicity. In vivo, SGLT2 was robustly expressed in kidney proximal tubule cells of heterozygous, but not null, mice. Phlorizin decreased GTTR uptake by kidney proximal tubule cells in Sglt2+/− mice, but not in Sglt2−/− mice. However, serum GTTR levels were elevated in Sglt2−/− mice compared to Sglt2+/− mice, and in phlorizin-treated Sglt2+/− mice compared to vehicle-treated Sglt2+/− mice. Loss of SGLT2 function by antagonism or by gene deletion did not affect gentamicin cochlear loading or auditory function. Phlorizin did not protect wild-type mice from kanamycin-induced ototoxicity. We conclude that SGLT2 can traffic gentamicin and contribute to gentamicin-induced cytotoxicity. PMID:25268124

  10. Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats

    PubMed Central

    Apaydin Yildirim, Betul; Kordali, Saban; Terim Kapakin, Kubra Asena; Yildirim, Fatih; Aktas Senocak, Esra; Altun, Serdar

    2017-01-01

    The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC. subsp. plicatum ethanol extract (HPE) against gentamicin-induced nephrotoxicity. Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material. They were formed into six groups containing 6 rats each and were allowed to adapt to laboratory conditions for 7 d. Group I: control, 5% DMSO intraperitoneal (i.p.); Group II: HPE 100 mg/(kg·d) i.p.; Group III: HPE 200 mg/(kg·d) i.p.; Group IV: gentamicin as 80 mg/(kg·d) i.p.; Group V: gentamicin as 80 mg/(kg·d) i.p.+HPE 100 mg/(kg·d) i.p.; and Group VI: gentamicin as 80 mg/(kg·d) i.p.+HPE 200 mg/(kg·d) i.p. for 8 d. Following treatment, serum, liver, and kidney tissues were used to assess blood urea nitrogen (BUN), creatinine, enzymatic and non-enzymatic antioxidants, and lipid peroxidation. Gentamicin significantly increased serum BUN, creatinin, and liver and kidney levels of malondialdehyde (MDA). It also decreased the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin, liver and kidney oxidant marker, and tubular necrosis as well as by an increase in antioxidant enzymes. It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats. As a result, these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters. PMID:28585426

  11. The effects of gentamicin and penicillin/streptomycin on the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes in manual patch clamp and multi-electrode array system.

    PubMed

    Hyun, Soo-Wang; Kim, Bo-Ram; Lin, Dan; Hyun, Sung-Ae; Yoon, Seong Shoon; Seo, Joung-Wook

    Cell culture media usually contains antibiotics including gentamicin or penicillin/streptomycin (PS) to protect cells from bacterial contamination. However, little is known about the effects of antibiotics on action potential and field potential parameters in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The present study examined the effects of gentamicin (10, 25, and 50μg/ml) and PS (50, 100, and 200U/μg/ml) on electrophysiological activity in spontaneously beating hiPSC-CMs using manual patch clamp and multi-electrode array. We also measured mRNA expression of cardiac ion channels in hiPSC-CMs grown in media with or without gentamicin (25μg/ml) using reverse transcription-polymerase chain reaction. We recorded action potential and field potential of hiPSC-CMs grown in the presence or absence of gentamicin or PS. We also observed action potential parameters in hiPSC-CMs after short-term treatment with these antibiotics. Changes in action potential and field potential parameters were observed in hiPSC-CMs grown in media containing gentamicin or PS. Treatment with PS also affected action potential parameters in hiPSC-CMs. In addition, the mRNA expression of cardiac sodium and potassium ion channels was significantly attenuated in hiPSC-CMs grown in the presence of gentamicin (25μg/ml). The present findings suggested that gentamicin should not be used in the culture media of hiPSC-CMs used for the measurement of electrophysiological parameters. Our findings also suggest that 100U/100μg/ml of PS are the maximum appropriate concentrations of these antibiotics for recording action potential waveform, because they did not influence action potential parameters in these cells. Copyright © 2017. Published by Elsevier Inc.

  12. Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

    PubMed Central

    Francescato, H.D.C.; Chierice, J.R.A.; Marin, E.C.S.; Cunha, F.Q.; Costa, R.S.; Silva, C.G.A.; Coimbra, T.M.

    2012-01-01

    Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg−1·day−1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein−1·h−1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation. PMID:22331137

  13. Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin.

    PubMed

    Francescato, H D C; Chierice, J R A; Marin, E C S; Cunha, F Q; Costa, R S; Silva, C G A; Coimbra, T M

    2012-03-01

    Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

  14. Evaluation of apoptotic markers in HEI-OC1 cells treated with gentamicin with and without the mitochondria-targeted antioxidant mitoquinone.

    PubMed

    Jadidian, Armon; Antonelli, Patrick J; Ojano-Dirain, Carolyn P

    2015-03-01

    Mitoquinone (MitoQ) attenuates aminoglycoside (AG)-induced upregulation of the proapoptotic molecules Bak and harakiri (Hrk) and decreases the percentage of apoptotic House Ear Institute Organ of Corti 1 (HEI-OC1) cells. The primary mechanism of AG ototoxicity is the formation of reactive oxygen species, which leads to hair cell death via apoptotic and nonapoptotic pathways. Antioxidants have been shown to protect against AG ototoxicity. Mitoquinone is a mitochondria-targeted derivative of the antioxidant ubiquinone. Thus, MitoQ may be more effective in preventing AG ototoxicity compared with untargeted antioxidants. Ribonucleic acid from untreated HEI-OC1 cells and cells exposed to gentamicin with and without preincubation with MitoQ, idebenone (IDB, an untargeted ubiquinone), or decylTPP (positive control) were used to assess gene expression of Bak and Hrk using real-time polymerase chain reaction. Protein expression of Bak and Hrk was determined by Western blotting. Annexin V assay using flow cytometry was performed to assess the percentage of apoptotic HEI-OC1 cells treated with gentamicin with and without preincubation with MitoQ, decylTPP, or IDB. Preincubation of HEI-OC1 cells with MitoQ significantly decreased the gentamicin-induced upregulation of Bak gene (p = 0.03) but not preincubation with IDB (p = 0.87). Harakiri levels were very low that relative quantification could not be carried out. Protein levels of Bak and Hrk were not different between treatments. Annexin V assay showed that gentamicin increased the percentage of apoptotic cells (p < 0.05) compared with control. However, the percentages of apoptotic cells in gentamicin-treated and cells pretreated with the antioxidants MitoQ or IDB were not different. Mitoquinone attenuated the gentamicin-induced upregulation of the Bak gene but not its product, the proapoptotic molecule Bak, and MitoQ did not significantly decrease the gentamicin-induced cell apoptosis in vitro. Further in vivo studies are needed to assess the clinical significance of these findings.

  15. In vitro activity of gentamicin as an adjunct to penicillin against biofilm group B Streptococcus.

    PubMed

    Ruppen, Corinne; Hemphill, Andrew; Sendi, Parham

    2017-02-01

    Group B Streptococcus (GBS) increasingly causes invasive disease in non-pregnant adults, particularly in elderly persons and those with underlying diseases. Combination therapy with penicillin plus gentamicin has been suggested for periprosthetic joint infection. The postulated synergism of this combination is based on experiments with planktonic bacteria. We aimed to assess the efficacy of this combination against sessile bacteria. Four different GBS strains were used. We compared results of MICs with those of minimal biofilm eradication concentrations (MBECs), applied chequerboard assays to the MBEC device and calculated the fractional inhibitory concentration index. Synergism was evaluated with time-kill assays against bacteria adherent to cement beads, using penicillin (0.048, 0.2 and 3 mg/L), gentamicin (4 and 12.5 mg/L) and a combination thereof. Results were evaluated via colony counting after sonication of beads and scanning electron microscopy. MBEC/MIC ratios were 2000-4000 for penicillin and 1-4 for gentamicin. In chequerboard assays, synergism was observed in all four isolates. In time-kill assays, penicillin and 12.5 mg/L gentamicin showed synergism in two isolates. In the other two isolates 12.5 mg/L gentamicin alone was as efficient as the combination therapy. These in vitro investigations show activity of 12.5 mg/L gentamicin, alone or as an adjunct to penicillin, against four strains of biofilm GBS. This concentration cannot be achieved in bone with systemic administration, but can be reached if administered locally. The combination of systemic penicillin plus local gentamicin indicates a potential application in orthopaedic-device-associated GBS infections. Studies with a larger number of strains are required to confirm our results. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Acquired Bartter syndrome following gentamicin therapy

    PubMed Central

    Singh, J.; Patel, M. L.; Gupta, K. K.; Pandey, S.; Dinkar, A.

    2016-01-01

    Aminoglycoside nephrotoxicity may manifest as nonoliguric renal failure or tubular dysfunction, such as Fanconi-like syndrome, Bartter-like syndrome (BS), or distal renal tubular acidosis. We report a case who developed severe renal tubular dysfunction on the the 7th day of gentamicin therapy, resulting in metabolic alkalosis, refractory hypokalemia, hypocalcemia, hypomagnesemia, and polyuria. The patient was diagnosed as a case of transient BS associated with gentamicin exposure. The patient recovered with conservative management. PMID:27942182

  17. Acquired Bartter syndrome following gentamicin therapy.

    PubMed

    Singh, J; Patel, M L; Gupta, K K; Pandey, S; Dinkar, A

    2016-01-01

    Aminoglycoside nephrotoxicity may manifest as nonoliguric renal failure or tubular dysfunction, such as Fanconi-like syndrome, Bartter-like syndrome (BS), or distal renal tubular acidosis. We report a case who developed severe renal tubular dysfunction on the the 7 th day of gentamicin therapy, resulting in metabolic alkalosis, refractory hypokalemia, hypocalcemia, hypomagnesemia, and polyuria. The patient was diagnosed as a case of transient BS associated with gentamicin exposure. The patient recovered with conservative management.

  18. Evaluation of nephroprotective activity of Musa paradisiaca L. in gentamicin-induced nephrotoxicity.

    PubMed

    Abbas, Khizar; Rizwani, Ghazala H; Zahid, Hina; Qadir, M Imran

    2017-05-01

    The objective of the study was to investigate the nephroprotective activity of methanolic extract of different morphological parts (bract, flower, trachea and tracheal fluid) of Musa paradisiaca L. (Family: Musaceae) against gentamicin-induced nephrotoxicity in mice. Gentamicin produced significant changes in biochemical (increased levels of blood urea nitrogen level, blood urea, and serum creatinine), and histological parameters in mice. Treatment with methanolic extract of bract (100 and 250mg/kg, b.w) and flowering stalk (trachea) (250 and 500mg/kg, b.w) significantly prevented biochemical and histological changes produced by gentamicin toxicity. The extracts of M. paradisiaca (bract and flowering stalk) could contribute a lead to discovery of a new drug for the treatment of drug-induced nephrotoxicity.

  19. Vergence-mediated modulation of the human horizontal vestibulo-ocular reflex is eliminated by a partial peripheral gentamicin lesion.

    PubMed

    Migliaccio, Americo A; Minor, Lloyd B; Carey, John P

    2004-11-01

    The angular vestibulo-ocular reflex normally has an increased response during vergence on a near target. Surgical unilateral vestibular deafferentation reduces the horizontal vestibulo-ocular reflex (VOR) in response to far target viewing and eliminates this vergence effect. Intratympanic gentamicin treatment reduces VOR gain during far viewing, but the reduction is less severe than that after unilateral vestibular deafferentation. We sought to determine how gentamicin would affect vergence-mediated modulation of the VOR. The VOR in response to passive head impulses in the horizontal plane while viewing a far (124 cm) or near (15 cm) target was evaluated in 11 subjects following intratympanic gentamicin treatment. Three of these subjects had also been tested immediately prior to receiving gentamicin. The impulses were low amplitude (approximately 20 degrees ), high velocity (approximately 150 degrees /s), high acceleration (approximately 3,000 degrees /s2) horizontal head rotations administered manually by the investigator. Binocular eye and head velocity were recorded using the scleral search coil technique. The VOR gain was defined as eye velocity divided by inverted head velocity. Prior to intratympanic gentamicin, the VOR gain during rotations to either side was symmetric and showed the same vergence-mediated increase. Following gentamicin, head impulses towards the untreated side yielded VOR gains of 0.91+/-0.12 while viewing a far target and 1.27+/-0.22 while viewing a near target, an increase of 33%. Head impulses towards the treated side produced a hypometric VOR with no increase between far and near viewing. The average latency of the VOR was 7.6+/-2.5 ms towards the untreated side for either near or far viewing and 20.7+/-13.1 ms towards the treated side for either near or far viewing. Our findings show that a peripheral lesion caused by gentamicin does not ablate the VOR but does eliminate a component of the vestibular signal that is necessary for vergence-mediated modulation of the VOR. Gentamicin has preferential toxicity for the hair cells in the central zone of the crista, where irregular afferents predominate. Our findings are consistent with the hypothesis that irregular afferents provide the necessary signal for vergence-mediated modulation of the VOR.

  20. Could edaravone prevent gentamicin ototoxicity? An experimental study.

    PubMed

    Turan, M; Ciğer, E; Arslanoğlu, S; Börekci, H; Önal, K

    2017-02-01

    Clinical application of gentamicin may cause nephrotoxicity and ototoxicity. Our study is the first study to investigate the protective effects of edaravone against the gentamicin-induced ototoxicity. We investigated the protective effect of intraperitoneal (i.p.) edaravone application against gentamicin-induced ototoxicity in guinea pigs. Fourteen guinea pigs were divided into two equal groups consisting of a control group and a study group. One-hundred sixty milligrams per kilogram subcutaneous gentamicin and 0.3 mL i.p. saline were applied simultaneously once daily to seven guinea pigs in the control group (group 1). One-hundred sixty milligrams per kilogram gentamicin was applied subcutaneously and 3 mg/kg edaravone was applied intraperitoneally once daily for 7 days simultaneously to seven guinea pigs in the study group (group 2). Following the drug application, auditory brainstem response measurements were performed for the left ear on the 3rd and 7th days. Hearing threshold values of the group 1 and group 2 measured in the 3rd day of the study were detected as 57.14 ± 4.88 and 82.86 ± 7.56, respectively. This difference was statistically significant ( p < 0.05). Hearing threshold values of the group 1 and group 2 measured in the 7th day of the study were detected as 87.14 ± 4.88 and 62.86 ± 4.88, respectively. This difference was statistically significant ( p < 0.05). A statistically significant difference between the average threshold values of edaravone-administered group 2 and that of group 1 without edaravone was found. These differences show that systemic edaravone administration could diminish ototoxic effects of gentamicin and the severity of the hearing loss.

  1. Reno-protective effects of propolis on gentamicin-induced acute renal toxicity in swiss albino mice.

    PubMed

    Aldahmash, Badr Abdullah; El-Nagar, Doaa Mohamed; Ibrahim, Khalid Elfakki

    Kidney is a vital organ which plays an important and irreplaceable role in detoxification and removal of xenobiotics. And therefore is vulnerable to develop various forms of injuries. Hence, making it immensely important to search for natural reno-protective compounds. This study therefore, aims to evaluate the reno-protective properties of propolis against gentamicin induced renal toxicity in mice. Three groups of 10 male mice each were used for this study. First group served as control, the second group (Gm group) was administered orally 80mg/kg body weight gentamicin for 7 days, and the third group (GmP group) was administered same dose of gentamicin with propolis (500mg/kg body weight) for 7 days. Various parameters were used to study the renal toxicity. Gentamicin caused significant renal damage as evident by the rise in BUN levels, diminished glomeruli hypocellularity, moderately dilated tubules, and mild loss of brush border, severe infiltration, extensive tubular degeneration and presence of tubular cast. Histochemistry results show presence of collagen and reticular fibres. Immunohistochemical reactions show kidney injury (Kim-1 gene-expression), oxidative stress (MDA gene-expression), and an increase in apoptosis (caspase-3 gene-expression). Co-administration of propolis with gentamicin showed significant decrease in BUN levels, appearance of healthy glomeruli with normal cellularity, reduction of tubular injury, decrease of collagen and reticular fibres deposition, reduction of apoptosis, kidney injury and oxidative stress. Results presented in this study clearly show the reno-protective role of propolis against gentamicin-induced toxicity on mice kidney. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  2. An experimental design approach to the preparation of pegylated polylactide-co-glicolide gentamicin loaded microparticles for local antibiotic delivery.

    PubMed

    Dorati, Rossella; DeTrizio, Antonella; Genta, Ida; Grisoli, Pietro; Merelli, Alessia; Tomasi, Corrado; Conti, Bice

    2016-01-01

    The present paper takes into account the DOE application to the preparation process of biodegradable microspheres for osteomyelitis local therapy. With this goal gentamicin loaded polylactide-co-glycolide-copolyethyleneglycol (PLGA-PEG) microspheres were prepared and investigated. Two preparation protocols (o/w and w/o/w) with different process conditions, and three PLGA-PEG block copolymers with different compositions of lactic and glycolic acids and PEG, were tested. A Design Of Experiment (DOE) screening design was applied as an approach to scale up manufacturing step. The results of DOE screening design confirmed that w/o/w technique, the presence of salt and the 15%w/v polymer concentration positively affected the EE% (72.1-97.5%), and span values of particle size distribution (1.03-1.23), while salt addition alone negatively affected the yield process. Process scale up resulted in a decrease of gentamicin EE% that can be attributed to the high volume of water used to remove PVA and NaCl residues. The results of in vitro gentamicin release study show prolonged gentamicin release up to three months from the microspheres prepared with salt addition in the dispersing phase; the behavior being consistent with their highly compact structure highlighted by scanning electron microscopy analysis. The prolonged release of gentamicin is maintained even after embedding the biodegradable microspheres into a thermosetting composite gel made of chitosan and acellular bovine bone matrix (Orthoss® granules), and the microbiologic evaluation demonstrated the efficacy of the gentamicin loaded microspheres on Escherichia coli. The collected results confirm the feasibility of the scale up of microsphere manufacturing process and the high potential of the microparticulate drug delivery system to be used for the local antibiotic delivery to bone.

  3. Doxycycline reduces nitric oxide production in guinea pig inner ears.

    PubMed

    Helling, Kai; Wodarzcyk, Karl; Brieger, Jürgen; Schmidtmann, Irene; Li, Huige; Mann, Wolf J; Heinrich, Ulf-Rüdiger

    2011-12-01

    Gentamicin application is an important therapeutic option to control vertigo spells in Ménière's disease. However, even in the case of low-dose intratympanic application, gentamicin might contribute to a pathological NO-increase leading to cochlear damage and hearing impairment. The study was performed to evaluate the nitric oxide (NO) reducing capacity of doxycycline in the inner ear after NO-induction by gentamicin. In a prospective animal study, a single dose of gentamicin (10mg/kg body weight) was injected intratympanically into male guinea pigs (n=48). The auditory brainstem responses (ABRs) were recorded prior to application and 3, 5 and 7 days afterwards. The organ of Corti and the lateral wall of 42 animals were isolated after 7 days and incubated separately for 6h in cell culture medium. Doxycycline was adjusted to organ cultures of 5 animals. Two NOS inhibitors, N(G)-Nitro-l-arginine methyl ester (l-NAME) and NG-monomethyl-l-arginine monoacetate (l-NMMA), were applied in three different concentrations to the organ cultures of 30 animals in total (5 animals per concentration). As controls, seven animals received no further substance except gentamicin. The NO-production was quantified by chemiluminescence. Additional six gentamicin-treated animals were used for immunohistochemical studies. The ABRs declined continuously from the first to the seventh day after gentamicin application. Doxycycline reduced NO-production in the lateral wall by 54% (p=.029) comparable to the effect of the applied nitric oxide inhibitors. In the organ of Corti, NO-production was reduced by about 41% showing no statistical significance in respect to great inter-animal variations. The application of doxycycline might offer a new therapeutic approach to prevent NO-induced cochlea damage through ototoxic substances. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Renoprotective effects of Andrographis paniculata (Burm. f.) Nees in rats

    PubMed Central

    Singh, Pratibha; Srivastava, Man Mohan

    2009-01-01

    Background Renal failure is an increasingly common condition with limited treatment options that is causing a major financial and emotional burden on the community. Andrographis paniculata is the plant used in Ayurveda for several remedies. Scientific evidence suggests its versatile biological functions that support its traditional use in the Orient. The plant is claimed to possess immunological, antibacterial, anti-inflammatory, antithrombotic, and hepatoprotective properties. But, to date, there is no study demonstrating the protective effect of A. paniculata on gentamicin-induced renal failure. The present study aims to highlight the first ever reported, antirenal failure activity of A. paniculata. Methods Male Wistar albino rats were divided into three groups: normal control, gentamicin control, and aqueous extract of A. paniculata (200 mg/kg, per oral (p.o.))-treated. The nephrotoxic model was induced by gentamicin (80 mg/kg, intraperitoeal (i.p.)). Blood samples were examined for serum creatinine, serum urea, and blood urea nitrogen after the 10 days of treatment. Results A gentamicin-induced nephrotoxic animal model was successfully prepared. Aqueous extract of A. paniculata attenuated the gentamicin-induced increase in serum creatinine, serum urea, and blood urea nitrogen levels by 176.92%, 106.27%, and 202.90%, respectively. Conclusion The present study reports that the aqueous extract (whole plant) of A. paniculata (Burm. f.) Nees exhibits a significant renoprotective effect in gentamicin-induced nephrotoxicity in male Wistar albino rats. PMID:19736602

  5. Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin.

    PubMed

    Ridolfi, Daniela M; Marcato, Priscyla D; Justo, Giselle Z; Cordi, Lívia; Machado, Daisy; Durán, Nelson

    2012-05-01

    Tretinoin (TRE) or all-trans retinoic acid is employed in the topical treatment of various skin diseases including acne and psoriasis. However, its use is strongly limited by side effects and high chemical instability. TRE encapsulation in nanostructured systems reduces these problems. Chitosan is a biopolymer that exhibits a number of interesting properties such as bioadhesion and antibacterial activity. The aim of this work was to prepare and characterize solid lipid nanoparticles (SLN) containing TRE, with and without addition of chitosan, to assess their in vitro cytotoxicity in keratinocytes and to evaluate their antibacterial activity against bacteria related to acne. SLN without (SLN-TRE) and with (SLN-chitosan-TRE) chitosan were prepared by hot high pressure homogenization. The hydrodynamic mean diameter and zeta potential were 162.7±1.4 nm and -31.9±2.0 mV for SLN-TRE, and 284.8±15.0 nm and 55.9±3.1 mV for SLN-chitosan-TRE. The SLN-chitosan-TRE exhibited high encapsulation efficiency, high physical stability in the tested period (one year), were not cytotoxic to keratinocytes and showed high antibacterial activity against P. acnes and S. aureus. Therefore chitosan-SLN can be good candidates to encapsulate TRE and to increase its therapeutic efficacy in the topical treatment of acne. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. An enzyme-free and label-free surface plasmon resonance biosensor for ultrasensitive detection of fusion gene based on DNA self-assembly hydrogel with streptavidin encapsulation.

    PubMed

    Guo, Bin; Wen, Bo; Cheng, Wei; Zhou, Xiaoyan; Duan, Xiaolei; Zhao, Min; Xia, Qianfeng; Ding, Shijia

    2018-07-30

    In this research, an enzyme-free and label-free surface plasmon resonance (SPR) biosensing strategy has been developed for ultrasensitive detection of fusion gene based on the heterogeneous target-triggered DNA self-assembly aptamer-based hydrogel with streptavidin (SA) encapsulation. In the presence of target, the capture probes (Cp) immobilized on the chip surface can capture the PML/RARα, forming a Cp-PML/RARα duplex. After that, the aptamer-based network hydrogel nanostructure is formed on the gold surface via target-triggered self-assembly of X shaped polymers. Subsequently, the SA can be encapsulated into hydrogel by the specific binding of SA aptamer, forming the complex with super molecular weight. Thus, the developed strategy achieves dramatic enhancement of the SPR signal. Using PML/RARα "S" subtype as model analyte, the developed biosensing method can detect target down to 45.22 fM with a wide linear range from 100 fM to 10 nM. Moreover, the high efficiency biosensing method shows excellent practical ability to identify the clinical PCR products of PML/RARα. Thus, this proposed strategy presents a powerful platform for ultrasensitive detection of fusion gene and early diagnosis and monitoring of disease. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Establishing the interfacial nano-structure and elemental composition of homeopathic medicines based on inorganic salts: a scientific approach.

    PubMed

    Temgire, Mayur Kiran; Suresh, Akkihebbal Krishnamurthy; Kane, Shantaram Govind; Bellare, Jayesh Ramesh

    2016-05-01

    Extremely dilute systems arise in homeopathy, which uses dilution factors 10(60), 10(400) and also higher. These amounts to potencies of 30c, 200c or more, those are far beyond Avogadro's number. There is extreme skepticism among scientists about the possibility of presence of starting materials due to these high dilutions. This has led modern scientists to believe homeopathy may be at its best a placebo effect. However, our recent studies on 30c and 200c metal based homeopathic medicines clearly revealed the presence of nanoparticles of starting metals, which were found to be retained due to the manufacturing processes involved, as published earlier.(9,10) Here, we use HR-TEM and STEM techniques to study medicines arising from inorganic salts as starting materials. We show that the inorganic starting materials are present as nano-scale particles in the medicines even at 1 M potency (having a large dilution factor of 10(2000)). Thus this study has extended our physicochemical studies of metal based medicines to inorganic based medicines, and also to higher dilution. Further, we show that the particles develop a coat of silica: these particles were seen embedded in a meso-microporous silicate layer through interfacial encapsulation. Similar silicate coatings were also seen in metal based medicines. Thus, metal and inorganic salt based homeopathic medicines retain the starting material as nanoparticles encapsulated within a silicate coating. On the basis of these studies, we propose a universal microstructural hypothesis that all types of homeopathic medicines consist of silicate coated nano-structures dispersed in the solvent. Copyright © 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  8. Comparison of topical mupirocin and gentamicin in the prevention of peritoneal dialysis-related infections: A systematic review and meta-analysis.

    PubMed

    Tsai, Chia-Chi; Yang, Po-Sheng; Liu, Chien-Liang; Wu, Chih-Jen; Hsu, Yi-Chiung; Cheng, Shih-Ping

    2018-01-01

    Topical antibiotics have been shown to reduce exit-site infection and peritonitis. The aim of this study was to compare infection rates between mupirocin and gentamicin. Multiple comprehensive databases were searched systematically to include relevant randomized controlled trials and observational studies. Pooled risk ratios (RRs) and 95% confidence intervals were calculated for the incidences of exit-site infection and peritonitis. Seven studies (mupirocin group n = 458, gentamicin group n = 448) were analyzed for exit-site infection. The risk of gram-positive exit-site infection was similar between the groups. Gram-negative exit-site infection rate was higher in the mupirocin group (RR = 2.125, P = 0.037). Six studies were assessed the peritonitis risk. There was no difference in the gram-positive and -negative peritonitis rate. Topical use of gentamicin is associated with fewer exit-site infections caused by gram-negative organisms. Gentamicin has comparable efficacy to mupirocin for peritonitis and gram-positive exit-site infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Comparison of disk diffusion and agar dilution methods for gentamicin susceptibility testing of Neisseria gonorrhoeae.

    PubMed

    Gianecini, Ricardo; Oviedo, Claudia; Irazu, Lucia; Rodríguez, Marcelo; Galarza, Patricia

    2018-03-29

    Gentamicin is a promising antibiotic for the treatment of multidrug-resistant gonorrhea. The aim of this study was to analyze the suitability and reliably of disk diffusion to monitor the susceptibility to gentamicin. We studied 237 Neisseria gonorrhoeae isolates obtained in 2013 and 2015. Reference MICs were correlated with inhibition zone diameters (in millimeters) of gentamicin 10 µg disks manufactured by BBL and Oxoid. The Pearson correlation between disk diffusion and agar dilution was r = -.68 (P < 0.001) for BBL disk and r = -.71 (P < 0.001) for Oxoid disk. No very major or major discrepancies were detected. However, a high percentage of minor discrepancies was observed (44.7%, BBL disk) and (21.9%, Oxoid disk). By adjusting the susceptible breakpoint to S ≥ 17 mm, the minor discrepancies rate was reduced to 19.4% (BBL disk) and 10.1% (Oxoid disk). The disk diffusion may be a screening method in clinical laboratories to detect the gentamicin susceptibility of N. gonorrhoeae. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Renal safety of short-term empiric gentamicin therapy in aged patients.

    PubMed

    Sia, Christopher Sb; Ananda-Rajah, Michelle R; Adler, Nikki R; Yi-Wei, Baey; Liew, Danny; Tong, Erica Y; Aung, Ar Kar

    2018-04-27

    To determine the incidence of acute kidney injury (AKI) in aged patients receiving empiric gentamicin therapy. Patients aged ≥65 years receiving gentamicin upon admission between 2013 and 2015 at two Australian hospitals were retrospectively studied. AKI was defined as a rise in creatinine by ≥50% and/or ≥26.5 μmol/L. Most patients (95%) received a single dose of gentamicin. The incidence of AKI was 15% (36/242 patients). A composite outcome of persistent kidney injury, requirement for renal replacement therapy or inpatient death in a patient with AKI occurred in 10 (4%) patients. Patients who developed AKI were older (median 80.5 vs 78 years, P = 0.03), had higher Charlson Co-morbidity Index (median 7 vs 5, P = 0.0004) and had more advanced chronic kidney disease at baseline (Stages IV and V) (OR 4.38, 95% confidence interval 1.45-13.2, P = 0.01). Empiric gentamicin use in patients with advancing age is associated with low rates of predominantly transient renal impairment. © 2018 AJA Inc.

  11. Gentamicin-loaded borate bioactive glass eradicates osteomyelitis due to Escherichia coli in a rabbit model.

    PubMed

    Xie, Zongping; Cui, Xu; Zhao, Cunju; Huang, Wenhai; Wang, Jianqiang; Zhang, Changqing

    2013-07-01

    The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli.

  12. Gentamicin-Loaded Borate Bioactive Glass Eradicates Osteomyelitis Due to Escherichia coli in a Rabbit Model

    PubMed Central

    Xie, Zongping; Cui, Xu; Zhao, Cunju; Huang, Wenhai; Wang, Jianqiang

    2013-01-01

    The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli. PMID:23629702

  13. Preparation, characterization, and in vitro release of gentamicin from coralline hydroxyapatite-alginate composite microspheres.

    PubMed

    Sivakumar, M; Rao, K Panduranga

    2003-05-01

    In this work, composite microspheres were prepared from bioactive ceramics such as coralline hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2)] granules, a biodegradable polymer, sodium alginate, and an antibiotic, gentamicin. Previously, we have shown a gentamicin release from coralline hydroxyapatite granules-chitosan composite microspheres. In the present investigation, we attempted to prepare composite microspheres containing coralline hydroxyapatite granules and sodium alginate by the dispersion polymerization technique with gentamicin incorporated by absorption method. The crystal structure of the composite microspheres was analyzed using X-ray powder diffractometer. Fourier transform infrared spectra clearly indicated the presence of per-acid of sodium alginate, phosphate, and hydroxyl groups in the composite microspheres. Scanning electron micrographs and optical micrographs showed that the composite microspheres were spherical in shape and porous in nature. The particle size of composite microspheres was analyzed, and the average size was found to be 15 microns. The thermal behavior of composite microspheres was studied using thermogravimetric analysis and differential scanning calorimetric analysis. The cumulative in vitro release profile of gentamicin from composite microspheres showed near zero order patterns. Copyright 2003 Wiley Periodicals, Inc.

  14. Preparation, characterization and in vitro release of gentamicin from coralline hydroxyapatite-gelatin composite microspheres.

    PubMed

    Sivakumar, M; Panduranga Rao, K

    2002-08-01

    Composite microspheres have been prepared from bioactive ceramics such as coralline hydroxyapatite [CHA, Ca10(PO4)6(OH)2] granules, a biodegradable polymer, gelatin and an antibiotic, gentamicin. In our earlier work, we have shown a gentamicin release from CHA granules--chitosan composite microspheres. In the present investigation, an attempt was made to prepare the composite microspheres containing coralline hydroxyapatite and gelatin (CHA-G), which were prepared by the dispersion polymerization technique and the gentamicin was incorporated by the absorption method. The crystal structure of the composite microspheres was analyzed using X-ray powder diffractometer. The Fourier transformed infrared spectrum clearly indicated the presence of amide and hydroxyl groups in the composite microspheres. Scanning electron micrographs and optical micrographs show that the composite microspheres are spherical in shape and porous in nature. The particle size of composite microspheres was analyzed and the average size was found to be 16 microm. The thermal behavior of composite microspheres was studied using thermogravimetric analysis and differential scanning calorimetric analysis. The cumulative in vitro release profile of gentamicin from composite microspheres showed near zero order patterns.

  15. Gentamicin Injection

    MedlinePlus

    ... treat certain serious infections that are caused by bacteria such as meningitis (infection of the membranes that ... medications called aminoglycoside antibiotics. It works by killing bacteria.Antibiotics such as gentamicin injection will not work ...

  16. Hybrid lipid-based nanostructures

    NASA Astrophysics Data System (ADS)

    Dayani, Yasaman

    Biological membranes serve several important roles, such as structural support of cells and organelles, regulation of ionic and molecular transport, barriers to non-mediated transport, contact between cells within tissues, and accommodation of membrane proteins. Membrane proteins and other vital biomolecules incorporated into the membrane need a lipid membrane to function. Due to importance of lipid bilayers and their vital function in governing many processes in the cell, the development of various models as artificial lipid membranes that can mimic cell membranes has become a subject of great interest. Using different models of artificial lipid membranes, such as liposomes, planar lipid bilayers and supported or tethered lipid bilayers, we are able to study many biophysical processes in biological membranes. The ability of different molecules to interact with and change the structure of lipid membranes can be also investigated in artificial lipid membranes. An important application of lipid bilayer-containing interfaces is characterization of novel membrane proteins for high throughput drug screening studies to investigate receptor-drug interactions and develop biosensor systems. Membrane proteins need a lipid bilayer environment to preserve their stability and functionality. Fabrication of materials that can interact with biomolecules like proteins necessitates the use of lipid bilayers as a mimic of cell membranes. The objective of this research is to develop novel hybrid lipid-based nanostructures mimicking biological membranes. Toward this aim, two hybrid biocompatible structures are introduced: lipid bilayer-coated multi-walled carbon nanotubes (MWCNTs) and hydrogel-anchored liposomes with double-stranded DNA anchors. These structures have potential applications in biosensing, drug targeting, drug delivery, and biophysical studies of cell membranes. In the first developed nanostructure, lipid molecules are covalently attached to the surfaces of MWCNTs, and then, using a sonication process, a uniform lipid bilayer that supports the incorporation of membrane proteins is formed. These bilayer-coated carbon nanotubes are highly dispersible and stable in aqueous solution, and they can be used in development of various biosensors and energy producing devices. In the other hybrid nanostructure, the lipid bilayer of a liposome is covalently anchored to a biocompatible poly(ethylene) glycol (PEG) hydrogel core using double-stranded DNA (dsDNA) linkers. Release studies shows that nano-size hydrogel-anchored liposomes are exceptionally stable, and they can be used as biomimetic model membranes that mimic the connectivity between the cytoskeleton and the plasma membrane. After lipid bilayer removal, dsDNA linkers can provide programmable nanogels decorated with oligonucleotides with potential sites for further molecular assembly. These stable nanostructures can be useful for oligonucleotide and drug delivery applications. The developed hydrogel-anchored liposomes are exploited for encapsulation and intracellular delivery of therapeutic peptide. Peptides with anti-cancer properties are successfully encapsulated in hydrogel core of pH-sensitive liposomes during rehydration process. Liposomes release their cargo at acidic pH. Confocal microscopy confirms the intracellular delivery of liposomes through an endocytotic pathway.

  17. Hierarchical structures based on self-assembling beta-hairpin peptides and their application as biomaterials and hybrid materials

    NASA Astrophysics Data System (ADS)

    Altunbas, Aysegul

    Self-assembly represents a robust and powerful paradigm for the bottom-up construction of nanostructures. Self-assembled peptide hydrogels are emerging as promising routes to novel multifunctional materials. The 20 amino acid MAX1and MAX8 peptides self-assemble into a three dimensional network of entangled, branched fibrils rich in beta-sheet secondary structure with a high density of lysine groups exposed on the fibril-surfaces. These hydrogels form self-supporting structures that shear thin upon application of shear and then immediately recover to a solid hydrogel upon cessation of shear which facilitates the local delivery of the hydrogel into a site in vivo. Templated condensation of silica precursors on self-assembled nanoscale peptide fibrils with various surface functionalities can be used to mimic biosilicification. This template-defined approach towards biomineralization was utilized for the controlled fabrication of 3D hybrid nanostructures. We report a study on the structure-property relationship of self-assembled peptide hydrogels where mineralization of individual fibrils through sol-gel chemistry was achieved. The nanostructure and consequent mechanical characteristics of these hybrid networks can be modulated by changing the stoichiometric parameters of the sol-gel process. Construction of such organic-inorganic hybrid networks by sol-gel processing of self-assembled peptide hydrogels has improved mechanical properties and resulted in materials with ˜ 3 orders of magnitude higher stiffness. The physical characterization of the hybrid networks via electron microscopy and small angle scattering is detailed and correlated with changes in the network mechanical behavior. The resultant high fidelity templating process suggests that the peptide substrate can be used to template the coating of other functional inorganic materials. Self-assembling peptide hydrogels encapsulating an anti-tumorigenic drug, curcumin, have been prepared and demonstrated to be an effective vehicle for the localized delivery of curcumin over sustained periods of time in vitro. The curcumin-hydrogel is prepared in-situ where curcumin encapsulation within the hydrogel network is accomplished concurrently with peptide self-assembly. Physical characterization methods and in vitro biological studies were used to demonstrate the effectiveness of curcumin-loaded beta-hairpin hydrogels as injectable agents for localized curcumin delivery. Notably, rheological characterization of the curcumin loaded hydrogel before and after shear flow have indicated solid-like properties even at high curcumin payloads. In vitro experiments with a medulloblastoma cell line confirm that the encapsulation of the curcumin within the hydrogel does not have an adverse effect on its bioactivity. Most importantly, the rate of curcumin release and its consequent therapeutic efficacy can be conveniently modulated by changing the morphological characteristics of the peptide hydrogel network. Lastly, MAX8 hydrogel cytocompatibility and biocompatibility was assessed with the future aim of utilizing this hydrogel as a scaffold in liver regeneration studies in rats. MAX8 hydrogel cytotoxity was evaluated using MC3T3-E1 and MG63 cell lines. Encapsulation, syringe delivery and subsequent viability of MG63 cells in hydrogels was also assessed to study the feasibility of using hydrogel/cell constructs as minimally invasive cell delivery vehicles. Biocompatibility was evaluated by monitoring inflammatory response induced by the MAX8 hydrogel via a subcutaneous mice model. Biocompatibility of MAX8 hydrogels at sites other than the subcutaneous region was also investigated using a cylindrical punch resection model in rat liver. The preliminary biocompatibility studies provide an elemental understanding of MAX8 hydrogel behavior in vivo.

  18. Carbenicillin and gentamicin in the treatment of Pseudomonas aeruginosa infection

    PubMed Central

    Yuce, Kemal; van Rooyen, C. E.

    1971-01-01

    The administration separately and sequentially of carbenicillin and gentamicin eradicated Ps. aeruginosa infections, during the period over which they were given, in all of 25 critically ill patients. Electron microscopy revealed differences in the action of these two antibiotics against Ps. aeruginosa in vitro. Culture studies showed synergism between them and destruction by gentamicin of the carbenicillin-induced long, filamentous form of the organism. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6 PMID:5004774

  19. Gas-Phase Combustion Synthesis of Nonoxide Nanoparticles in Microgravity

    NASA Technical Reports Server (NTRS)

    Axelbaum, R. L.; Kumfer, B. M.; Sun, Z.; Chao, B. H.

    2001-01-01

    Gas-phase combustion synthesis is a promising process for creating nanoparticles for the growing nanostructure materials industry. The challenges that must be addressed are controlling particle size, preventing hard agglomerates, maintaining purity, and, if nonoxides are synthesized, protecting the particles from oxidation and/or hydrolysis during post-processing. Sodium-halide Flame Encapsulation (SFE) is a unique methodology for producing nonoxide nanoparticles that addresses these challenges. This flame synthesis process incorporates sodium and metal-halide chemistry, resulting in nanoparticles that are encapsulated in salt during the early stages of their growth in the flame. Salt encapsulation has been shown to allow control of particle size and morphology, while serving as an effective protective coating for preserving the purity of the core particles. Metals and compounds that have been produced using this technology include Al, W, Ti, TiB2, AlN, and composites of W-Ti and Al-AlN. Oxygen content in SFE synthesized nano- AlN has been measured by neutron activation analysis to be as low as 0.54wt.%, as compared to over 5wt.% for unprotected AlN of comparable size. The overall objective of this work is to study the SFE process and nano-encapsulation so that they can be used to produce novel and superior materials. SFE experiments in microgravity allow the study of flame and particle dynamics without the influence of buoyancy forces. Spherical sodium-halide flames are produced in microgravity by ejecting the halide from a spherical porous burner into a quiescent atmosphere of sodium vapor and argon. Experiments are performed in the 2.2 sec Drop Tower at the NASA-Glenn Research Center. Numerical models of the flame and particle dynamics were developed and are compared with the experimental results.

  20. 1-D Metal Nanobead Arrays within Encapsulated Nanowires via a Red-Ox-Induced Dewetting: Mechanism Study by Atom-Probe Tomography.

    PubMed

    Sun, Zhiyuan; Tzaguy, Avra; Hazut, Ori; Lauhon, Lincoln J; Yerushalmi, Roie; Seidman, David N

    2017-12-13

    Metal nanoparticle arrays are excellent candidates for a variety of applications due to the versatility of their morphology and structure at the nanoscale. Bottom-up self-assembly of metal nanoparticles provides an important complementary alternative to the traditional top-down lithography method and makes it possible to assemble structures with higher-order complexity, for example, nanospheres, nanocubes, and core-shell nanostructures. Here we present a mechanism study of the self-assembly process of 1-D noble metal nanoparticles arrays, composed of Au, Ag, and AuAg alloy nanoparticles. These are prepared within an encapsulated germanium nanowire, obtained by the oxidation of a metal-germanium nanowire hybrid structure. The resulting structure is a 1-D array of equidistant metal nanoparticles with the same diameter, the so-called nanobead (NB) array structure. Atom-probe tomography and transmission electron microscopy were utilized to investigate the details of the morphological and chemical evolution during the oxidation of the encapsulated metal-germanium nanowire hybrid-structures. The self-assembly of nanoparticles relies on the formation of a metal-germanium liquid alloy and the migration of the liquid alloy into the nanowire, followed by dewetting of the liquid during shape-confined oxidation where the liquid column breaks-up into nanoparticles due to the Plateau-Rayleigh instability. Our results demonstrate that the encapsulating oxide layer serves as a structural scaffold, retaining the overall shape during the eutectic liquid formation and demonstrates the relationship between the oxide mechanical properties and the final structural characteristics of the 1-D arrays. The mechanistic details revealed here provide a versatile tool-box for the bottom-up fabrication of 1-D arrays nanopatterning that can be modified for multiple applications according to the RedOx properties of the material system components.

  1. Bioadhesive chitosan-coated cyclodextrin-based superamolecular nanomicelles to enhance the oral bioavailability of doxorubicin

    NASA Astrophysics Data System (ADS)

    Liu, Yuhai; Zhai, Yinglei; Han, Xiaopeng; Liu, Xiaohong; Liu, Wanjun; Wu, Chunnuan; Li, Lin; Du, Yuqian; Lian, He; Wang, Yongjun; He, Zhonggui; Sun, Jin

    2014-10-01

    In order to improve the oral bioavailability of doxorubicin (Dox), a novel bioadhesive nanomicelle based on host-guest interaction was developed in this study. Hyaluronic acid-linked β-cyclodextrin (HA-CD) was synthesized. The primary nanomicelles were formed through the self-assemble of HA-CD and retinoic acid (RA) which was included as the hydrophobic core to anchor CD cavity by host-guest interaction. Chitosan (CS) was then coated on the surface of primary nanomicelles by ionic interaction with the negatively charged HA. The critical micellar concentration of HA-CD-RA was as low as 22.5 μg/mL. Dox was successfully encapsulated into the hydrophobic core of CS-coated HA-CD-RA nanomicelles (CS/HA-CD-RA-Dox), with encapsulation efficiency as high as 89.2 %. The CS/HA-CD-RA-Dox particle size was 234 nm and was stable over 30 days. In vitro Dox release showed that CS/HA-CD-RA nanomicelles were more sustained than HA-CD-RA nanomicelles, and Dox encapsulated into CS-coated nanomicelles was stable at low pH. The in situ single pass intestinal perfusion revealed that encapsulation of Dox into CS/HA-CD-RA nanomicelles could significantly improve the intestinal permeability of Dox. The mucoadhesion results indicated that the retention percentage of CS/HA-CD-RA nanomicelles was significantly higher than that of HA-CD-RA nanomicelles in gastrointestinal tract. In vivo pharmacokinetic study revealed that AUC(0-∞) of CS/HA-CD-RA nanomicelles was about fourfold higher than that of Dox solution. The present study suggested that CS/HA-CD-RA nanomicelles as biodegradable, biocompatible, and bioadhesive nanostructure can be a promising nanocarrier in improving the bioavailability of anticancer drugs to facilitate the oral chemotherapy.

  2. Graphene-bonded and -encapsulated si nanoparticles for lithium ion battery anodes.

    PubMed

    Wen, Yang; Zhu, Yujie; Langrock, Alex; Manivannan, Ayyakkannu; Ehrman, Sheryl H; Wang, Chunsheng

    2013-08-26

    Silicon (Si) has been considered a very promising anode material for lithium ion batteries due to its high theoretical capacity. However, high-capacity Si nanoparticles usually suffer from low electronic conductivity, large volume change, and severe aggregation problems during lithiation and delithiation. In this paper, a unique nanostructured anode with Si nanoparticles bonded and wrapped by graphene is synthesized by a one-step aerosol spraying of surface-modified Si nanoparticles and graphene oxide suspension. The functional groups on the surface of Si nanoparticles (50-100 nm) not only react with graphene oxide and bind Si nanoparticles to the graphene oxide shell, but also prevent Si nanoparticles from aggregation, thus contributing to a uniform Si suspension. A homogeneous graphene-encapsulated Si nanoparticle morphology forms during the aerosol spraying process. The open-ended graphene shell with defects allows fast electrochemical lithiation/delithiation, and the void space inside the graphene shell accompanied by its strong mechanical strength can effectively accommodate the volume expansion of Si upon lithiation. The graphene shell provides good electronic conductivity for Si nanoparticles and prevents them from aggregating during charge/discharge cycles. The functionalized Si encapsulated by graphene sample exhibits a capacity of 2250 mAh g⁻¹ (based on the total mass of graphene and Si) at 0.1C and 1000 mAh g⁻¹ at 10C, and retains 85% of its initial capacity even after 120 charge/discharge cycles. The exceptional performance of graphene-encapsulated Si anodes combined with the scalable and one-step aerosol synthesis technique makes this material very promising for lithium ion batteries. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. A protein/antibiotic releasing poly(lactic-co-glycolic acid)/lecithin scaffold for bone repair applications.

    PubMed

    Shi, Xuetao; Wang, Yingjun; Ren, Li; Huang, Wei; Wang, Dong-An

    2009-05-21

    Novel poly(lactic-co-glycolic acid) (PLGA)-hybridizing-lecithin scaffolds loaded with drug or protein were prepared with water/oil/water techniques and sintering microspheres technique. In such fabricated composite scaffolds (abbreviated "PLGA/Lec-SMS"), the introduction of lecithin component has been proven capable of largely enhancing Gentamicin (GS) and protein (Bovine Serum Albumin) encapsulation efficiency. The in vitro GS and BSA releasing profiles of PLGA/Lec-SMS system were plotted basing over 60 days' and 18 days' data collection, respectively. It indicates a sustained releasing tendency despite a burst at the very beginning. The antibacterial properties of GS-laden scaffolds were determined in vitro, and the antibacterial activity of scaffolds was enhanced by incorporating lecithin into PLGA bulks. Additionally, mesenchymal stem cells (MSCs) were seeded onto PLGA-SMS and PLGA/Lec-SMS in vitro. The outcome confirmed PLGA/Lec(5%)-SMS functions to improve MSC proliferation and also to enhance general ALP production and calcium secretion which is the vital markers for osteogenesis. In conclusion, this newly designed antibiotic releasing PLGA/Lec-SMS is promising for bone-repairing therapeutics.

  4. Use of the interior cavity of the P22 capsid for site-specific initiation of atom-transfer radical polymerization with high-density cargo loading

    NASA Astrophysics Data System (ADS)

    Lucon, Janice; Qazi, Shefah; Uchida, Masaki; Bedwell, Gregory J.; Lafrance, Ben; Prevelige, Peter E.; Douglas, Trevor

    2012-10-01

    Virus-like particles (VLPs) have emerged as important and versatile architectures for chemical manipulation in the development of functional hybrid nanostructures. Here we demonstrate a successful site-selective initiation of atom-transfer radical polymerization reactions to form an addressable polymer constrained within the interior cavity of a VLP. Potentially, this protein-polymer hybrid of P22 and cross-linked poly(2-aminoethyl methacrylate) could be useful as a new high-density delivery vehicle for the encapsulation and delivery of small-molecule cargos. In particular, the encapsulated polymer can act as a scaffold for the attachment of small functional molecules, such as fluorescein dye or the magnetic resonance imaging (MRI) contrast agent Gd-diethylenetriaminepentacetate, through reactions with its pendant primary amine groups. Using this approach, a significant increase in the labelling density of the VLP, compared to that of previous modifications of VLPs, can be achieved. These results highlight the use of multimeric protein-polymer conjugates for their potential utility in the development of VLP-based MRI contrast agents with the possibility of loading other cargos.

  5. Enhanced cellular transport and drug targeting using dendritic nanostructures

    NASA Astrophysics Data System (ADS)

    Kannan, R. M.; Kolhe, Parag; Kannan, Sujatha; Lieh-Lai, Mary

    2003-03-01

    Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorable, peripheral' functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug delivery. The large density of end groups can also be tailored to create enhanced affinity to targeted cells, and can also encapsulate drugs and deliver them in a controlled manner. We are developing tailor-modified dendritic systems for drug delivery. Synthesis, drug/ligand conjugation, in vitro cellular and in vivo drug delivery, and the targeting efficiency to the cell are being studied systematically using a wide variety of experimental tools. Results on PAMAM dendrimers and polyol hyperbranched polymers suggest that: (1) These materials complex/encapsulate a large number of drug molecules and release them at tailorable rates; (2) The drug-dendrimer complex is transported very rapidly through a A549 lung epithelial cancel cell line, compared to free drug, perhaps by endocytosis. The ability of the drug-dendrimer-ligand complexes to target specific asthma and cancer cells is currently being explored using in vitro and in vivo animal models.

  6. Microbubble-Triggered Spontaneous Separation of Transparent Thin Films from Substrates Using Evaporable Core-Shell Nanocapsules.

    PubMed

    Son, Intae; Lee, Byungsun; Kim, Jae Hong; Kim, Chunho; Yoo, Ji Yong; Ahn, Byung Wook; Hwang, Jeongho; Lee, Jonghyuk; Lee, Jun Hyup

    2018-05-23

    The spontaneous separation of a polymer thin film from a substrate is an innovative technology that will enable material recycling and reduce manufacturing cost in the film industry, and this can be applied in a wide range of applications, from optical films to wearable devices. Here, we present an unprecedented spontaneous strategy for separating transparent polymer films from substrates on the basis of microbubble generation using nanocapsules containing an evaporable material. The core-shell nanocapsules are prepared from poly(methyl methacrylate)-polyethyleneimine nanoparticles via the encapsulation of methylcyclohexane (MCH). A spherical nanostructure with a vaporizable core is obtained, with the heat-triggered gas release ability leading to the formation of microbubbles. Our separation method applied to transparent polymer films doped with a small amount of the nanocapsules encapsulating evaporable MCH enables spontaneous detachment of thin films from substrates via vacuum-assisted rapid vaporization of MCH over a short separation time, and clear detachment of the film is achieved with no deterioration of the inherent optical transparency and adhesive property compared to a pristine film.

  7. Polyaniline nanowire array encapsulated in titania nanotubes as a superior electrode for supercapacitors

    NASA Astrophysics Data System (ADS)

    Xie, Keyu; Li, Jie; Lai, Yanqing; Zhang, Zhi'an; Liu, Yexiang; Zhang, Guoge; Huang, Haitao

    2011-05-01

    Conducting polymer with 1D nanostructure exhibits excellent electrochemical performances but a poor cyclability that limits its use in supercapacitors. In this work, a novel composite electrode made of polyaniline nanowire-titania nanotube array was synthesized via a simple and inexpensive electrochemical route by electropolymerizing aniline onto an anodized titania nanotube array. The specific capacitance was as high as 732 F g-1 at 1 A g-1, which remained at 543 F g-1 when the current density was increased by 20 times. 74% of the maximum energy density (36.6 Wh kg-1) was maintained even at a high power density of 6000 W kg-1. An excellent long cycle life of the electrode was observed with a retention of ~86% of the initial specific capacitance after 2000 cycles. The good electrochemical performance was attributed to the unique microstructure of the electrode with disordered PANI nanowire arrays encapsulated inside the TiO2 nanotubes, providing high surface area, fast diffusion path for ions and long-term cycle stability. Such a nanocomposite electrode is attractive for supercapacitor applications.

  8. Facile Synthesis of Coaxial CNTs/MnOx-Carbon Hybrid Nanofibers and Their Greatly Enhanced Lithium Storage Performance.

    PubMed

    Yang, Zunxian; Lv, Jun; Pang, Haidong; Yan, Wenhuan; Qian, Kun; Guo, Tailiang; Guo, Zaiping

    2015-12-01

    Carbon nanotubes (CNTs)/MnOx-Carbon hybrid nanofibers have been successfully synthesized by the combination of a liquid chemical redox reaction (LCRR) and a subsequent carbonization heat treatment. The nanostructures exhibit a unique one-dimensional core/shell architecture, with one-dimensional CNTs encapsulated inside and a MnOx-carbon composite nanoparticle layer on the outside. The particular porous characteristics with many meso/micro holes/pores, the highly conductive one-dimensional CNT core, as well as the encapsulating carbon matrix on the outside of the MnOx nanoparticles, lead to excellent electrochemical performance of the electrode. The CNTs/MnOx-Carbon hybrid nanofibers exhibit a high initial reversible capacity of 762.9 mAhg(-1), a high reversible specific capacity of 560.5 mAhg(-1) after 100 cycles, and excellent cycling stability and rate capability, with specific capacity of 396.2 mAhg(-1) when cycled at the current density of 1000 mAg(-1), indicating that the CNTs/MnOx-Carbon hybrid nanofibers are a promising anode candidate for Li-ion batteries.

  9. Facile Synthesis of Coaxial CNTs/MnOx-Carbon Hybrid Nanofibers and Their Greatly Enhanced Lithium Storage Performance

    PubMed Central

    Yang, Zunxian; Lv, Jun; Pang, Haidong; Yan, Wenhuan; Qian, Kun; Guo, Tailiang; Guo, Zaiping

    2015-01-01

    Carbon nanotubes (CNTs)/MnOx-Carbon hybrid nanofibers have been successfully synthesized by the combination of a liquid chemical redox reaction (LCRR) and a subsequent carbonization heat treatment. The nanostructures exhibit a unique one-dimensional core/shell architecture, with one-dimensional CNTs encapsulated inside and a MnOx-carbon composite nanoparticle layer on the outside. The particular porous characteristics with many meso/micro holes/pores, the highly conductive one-dimensional CNT core, as well as the encapsulating carbon matrix on the outside of the MnOx nanoparticles, lead to excellent electrochemical performance of the electrode. The CNTs/MnOx-Carbon hybrid nanofibers exhibit a high initial reversible capacity of 762.9 mAhg−1, a high reversible specific capacity of 560.5 mAhg−1 after 100 cycles, and excellent cycling stability and rate capability, with specific capacity of 396.2 mAhg−1 when cycled at the current density of 1000 mAg−1, indicating that the CNTs/MnOx-Carbon hybrid nanofibers are a promising anode candidate for Li-ion batteries. PMID:26621615

  10. Effect of squalane on mebendazole-loaded Compritol® nanoparticles.

    PubMed

    Graves, Richard A; Ledet, Grace A; Nation, Cedric A; Pramar, Yashoda V; Bostanian, Levon A; Mandal, Tarun K

    2015-01-01

    The objective of this study is to develop nanostructured lipid formulations of Compritol for the delivery of mebendazole. The formulations were prepared with Compritol 888 ATO, squalane, and Pluronic F68. Nine batches with different amounts of modifier, squalane, and drug were prepared. The formulations were characterized by evaluating particle size, morphology, and zeta potential. The thermal properties of the formulations were analyzed by differential scanning calorimetry (DSC). The encapsulation efficiency of each formulation and the drug release rates from each formulation were quantified by UPLC. The particles were spherical and had median particle sizes between 300 and 600 nm (50th percentile). A linear relationship was observed between Compritol/squalane composition and the melting point of the mixture. The DSC scans of the formulations revealed some recrystallization of the drug from the formulations, and the amount of recrystallization correlated with the amount of squalane in the formulation. Approximately, 70% efficiency of encapsulation was observed in the formulations with 30% (w/w) squalane, and these formulations also had faster dissolution rates compared to the other formulations. Overall, the formulations with 30% squalane are the preferred formulation for future testing.

  11. Effects of gentamicin and monomer on bone. An in vitro study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pedersen, J.G.; Lund, B.

    1988-01-01

    Gentamicin-loaded bone cement is used with increasing frequency in primary and revision arthroplasty. Considering the high local concentration and the well-known toxic effect of gentamicin on the kidney, a similar inhibiting effect on bone tissue might be expected. In a series of in vitro studies using paired mouse calvaries cultured for 2 days, the authors found a dose-dependent decrease in the release of previously incorporated calcium-45 (UVCa) or tritiated proline and a decrease in alkaline phosphatase activity. In combination with methylmethacrylate, a small additional reduction in UVCa release and a marked decrease in alkaline phosphatase activity were recorded. These resultsmore » indicate that released gentamicin and monomer from antibiotic-supplemented bone cement depresses bone turnover and might thus play an important part in the pathogenesis of loosening.« less

  12. Neurotrophic and antioxidant effects of silymarin comparable to 4-methylcatechol in protection against gentamicin-induced ototoxicity in guinea pigs.

    PubMed

    Draz, Eman I; Abdin, Amany A; Sarhan, Naglaa I; Gabr, Takwa A

    2015-04-01

    Despite that gentamicin is a very effective aminoglycoside, its potential ototoxicity which is of irreversible nature makes a challenge and limitation for its use. This study was designed to investigate possible neurotrophic and antioxidant effects of silymarin comparable to 4-methylcatechol in protection against gentamicin-induced ototoxicity. Twenty pigmented guinea pigs were divided into four equal groups, where group I served as normal control group. The other groups received gentamicin (120 mg/kg/day, ip) for 19 days where group II given vehicle of 1% CMC, group III and group IV were pre-treated 2h before gentamicin by 4-methylcatechol (10 μg/kg, ip) and silymarin (100mg/kg, oral gavage), respectively. The main findings indicated that silymarin exhibited restoration of nerve growth factor (NGF) levels and increased tropomyosin-related kinase receptors-A (Trk-A) m-RNA expression in cochlear tissue and preservation of hair cells of organ of Corti by scanning electron microscopy (SEM) with significant decrease in auditory brainstem response (ABR) threshold compared to 4-methylcatechol. Only silymarin caused significant amelioration in oxidative stress state by reducing malondialdehyde (MDA) levels and increasing catalase activity. Silymarin exerts superiority over 4-methylcatechol when recommended as protective agent against gentamicin ototoxicity based on its efficient neurotrophic and antioxidant activities. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  13. Proteomic Candidate Biomarkers of Drug-Induced Nephrotoxicity in the Rat

    PubMed Central

    Rouse, Rodney; Siwy, Justyna; Mullen, William; Mischak, Harald; Metzger, Jochen; Hanig, Joseph

    2012-01-01

    Improved biomarkers of acute nephrotoxicity are coveted by the drug development industry, regulatory agencies, and clinicians. In an effort to identify such biomarkers, urinary peptide profiles of rats treated with two different nephrotoxins were investigated. 493 marker candidates were defined that showed a significant response to cis-platin comparing a cis-platin treated cohort to controls. Next, urine samples from rats that received three consecutive daily doses of 150 or 300 mg/kg gentamicin were examined. 557 potential biomarkers were initially identified; 108 of these gentamicin-response markers showed a clear temporal response to treatment. 39 of the cisplatin-response markers also displayed a clear response to gentamicin. Of the combined 147 peptides, 101 were similarly regulated by gentamicin or cis-platin and 54 could be identified by tandem mass spectrometry. Most were collagen type I and type III fragments up-regulated in response to gentamicin treatment. Based on these peptides, classification models were generated and validated in a longitudinal study. In agreement with histopathology, the observed changes in classification scores were transient, initiated after the first dose, and generally persistent over a period of 10–20 days before returning to control levels. The data support the hypothesis that gentamicin-induced renal toxicity up-regulates protease activity, resulting in an increase in several specific urinary collagen fragments. Urinary proteomic biomarkers identified here, especially those common to both nephrotoxins, may serve as a valuable tool to investigate potential new drug candidates for the risk of nephrotoxicity. PMID:22509332

  14. Dose rates of antimicrobial substances in boar semen preservation-time to establish new protocols.

    PubMed

    Schulze, M; Grobbel, M; Riesenbeck, A; Brüning, S; Schaefer, J; Jung, M; Grossfeld, R

    2017-06-01

    To achieve a standardized number of spermatozoa in the final AI dose, varying amounts of extender fluid with a fixed concentration of antimicrobial substances are currently added to boar ejaculates. This practice ignores the different degrees of dilution of the antimicrobials in the end product. In calculating the final concentration of gentamicin in AI doses from 27,538 processed boar ejaculates, we demonstrated varying gentamicin concentrations in the resultant extended boar semen samples. The median concentration was 220.37 mg/L. In 25 of the samples (0.09%), the gentamicin concentration fell below 5 mg/L, which is close to or below the epidemiological cut-off value for many bacteria. We calculated the minimum inhibitory concentration of gentamicin for bacteria isolated from raw and extended ejaculates. Five of the isolates from extended ejaculates exceeded the maximum test concentration of 512 mg/L. As a result, we are presenting an alternative method of boar semen preservation whereby a particular combination of gentamicin concentrate and antibiotic-free extender is incorporated that standardizes the antibiotic concentration in the diluted semen. The addition of standardized antibiotic concentrations did not negatively affect sperm quality when compared to the use of ready-to-use extenders. In conclusion, an end volume-based and standardized addition of gentamicin to boar ejaculates can be a helpful alternative to prevent insufficient dosage of antibiotics in liquid preserved boar semen without affecting semen quality. © 2017 Blackwell Verlag GmbH.

  15. Pharmacokinetic Studies of Tobramycin and Gentamicin

    PubMed Central

    Simon, V. K.; Mösinger, E. U.; Malerczy, V.

    1973-01-01

    Broth dilution susceptibility tests of 100 isolates of Pseudomonas aeruginosa and 101 isolates of Staphylococcus aureus against tobramycin (formerly nebramycin factor 6) and gentamicin showed that tobramycin was more effective against P. aeruginosa and less effective against S. aureus. The minimal inhibitory concentration of tobramycin against the Pseudomonas sp. isolates that required 5 μg of gentamicin per ml for inhibition ranged from 0.63 to 0.31 μg/ml. Peak concentrations in the blood of 10 healthy adults after intramuscular injection of 80 and 40 mg of tobramycin averaged 3.7 ± 0.62 and 2.4 ± 0.27 μg/ml, and declined to 0.56 ± 0.05 and 0.26 ± 0.02 μg/ml, respectively, after 6 h. The urine recovery averaged 60%. The half-life was 1.6 h. During continuous intravenous infusion of tobramycin and gentamicin (infusion rate 6.6 mg per h), blood levels at steady state were 0.94 ± 0.10 and 1.04 ± 0.06 μg/ml, respectively. For both antibiotics, the calculated distribution volume ranged from 15 to 17 liters. The renal clearance to tobramycin averaged 76% and that of gentamicin averaged 85% of the total clearance, indicating that the drugs are primarily eliminated by the kidneys. The present results suggest that tobramycin may be more successful in the treatment of Pseudomonas infections than gentamicin at the same dosage (80 mg intramuscularly three to four times daily). PMID:4208289

  16. Degradation and recovery of the external quantum efficiency of organic photovoltaic structure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lazarev, V. V., E-mail: lbf@ns.crys.ras.ru; Blinov, L. M.; Yudin, S. G.

    2017-03-15

    The photosensitivity of a mixed composition of donor CuPc and acceptor C{sub 60}, its degradation in time (for 16 months), and partial recovery (issues that were out of consideration previously) have been investigated. The sample is a simple nanostructure without encapsulation (quartz–SnO{sub 2}–CuPc:C{sub 60}–Al), the degradation of which is easier to analyze. It is shown that the process under study involves two mechanisms: slow (because of the decrease in the carrier lifetime) and relatively fast (because of the decrease in the internal field) degradations of the sample photosensitivity.

  17. Effectiveness and Toxicity of Gentamicin in an Experimental Model of Pyelonephritis: Effect of the Time of Administration

    PubMed Central

    LeBrun, Michel; Grenier, Louis; Gourde, Pierrette; Bergeron, Michel G.; Labrecque, Gaston; Beauchamp, Denis

    1999-01-01

    Temporal variations in the renal toxicity of aminoglycosides have been reported for experimental animals as well as for humans. In fact, maximal renal toxicity of aminoglycosides was observed when the drug was given during the rest period, while a lower toxicity was observed when the drug was injected during the activity period. The aim of the present study was to evaluate temporal variations in the effectiveness and renal toxicity of gentamicin in an experimental model of pyelonephritis in rats. The experiments were carried out with female Sprague-Dawley rats (185 to 250 g). They had free access to food and water throughout the study and were maintained on a 14-h light–10-h dark cycle. Animals were divided into four groups corresponding to the respective time of induction of pyelonephritis and treatment: 0700, 1300, 1900, and 0100 h. Pyelonephritis was induced by a direct inoculation of Escherichia coli (107 to 108 CFU) in the left kidney. Animals were treated for 3 and 7 days with a single daily dose of gentamicin (20 and 40 mg/kg of body weight, respectively) or saline (NaCl, 0.9%) at either 0700, 1300, 1900, or 0100 h. Animals treated at 0100 h for 3 days with gentamicin (20 mg/kg) showed a significantly lower number of bacteria in their kidneys than did all other groups (P < 0.01). After 7 days of treatment, the efficacy, evaluated by the log CFU per gram of tissue and by the percentage of sterilized kidneys, was also higher when gentamicin was administered at 0100 h. The β-galactosidase and the N-acetyl-β-d-glucosaminidase activities were significantly higher in urine of rats given gentamicin at 1300 h than in urine of rats treated at another time of day (P < 0.05). Gentamicin injected at 1300 h induced a significantly greater increase of [3H]thymidine incorporation into DNA of renal cortex (P < 0.01), a significantly greater inhibition of sphingomyelinase activity (P < 0.05), and significantly more histopathological lesions than the same dose injected at another time of the day. Creatinine and blood urea nitrogen levels in serum were significantly higher (P < 0.05) and the creatinine clearance was significantly lower (P < 0.05) when gentamicin was injected at 1300 h than when it was injected at another time of day. Our data suggest temporal variations in both the toxicity and the effectiveness of gentamicin, the drug being more effective and less toxic when injected during the activity period of the animals. PMID:10223909

  18. Design of hybrid two-dimensional and three-dimensional nanostructured arrays for electronic and sensing applications

    NASA Astrophysics Data System (ADS)

    Ko, Hyunhyub

    This dissertation presents the design of organic/inorganic hybrid 2D and 3D nanostructured arrays via controlled assembly of nanoscale building blocks. Two representative nanoscale building blocks such as carbon nanotubes (one-dimension) and metal nanoparticles (zero-dimension) are the core materials for the study of solution-based assembly of nanostructured arrays. The electrical, mechanical, and optical properties of the assembled nanostructure arrays have been investigated for future device applications. We successfully demonstrated the prospective use of assembled nanostructure arrays for electronic and sensing applications by designing flexible carbon nanotube nanomembranes as mechanical sensors, highly-oriented carbon nanotubes arrays for thin-film transistors, and gold nanoparticle arrays for SERS chemical sensors. In first section, we fabricated highly ordered carbon nanotube (CNT) arrays by tilted drop-casting or dip-coating of CNT solution on silicon substrates functionalized with micropatterned self-assembled monolayers. We further exploited the electronic performance of thin-film transistors based on highly-oriented, densely packed CNT micropatterns and showed that the carrier mobility is largely improved compared to randomly oriented CNTs. The prospective use of Raman-active CNTs for potential mechanical sensors has been investigated by studying the mechano-optical properties of flexible carbon nanotube nanomembranes, which contain freely-suspended carbon nanotube array encapsulated into ultrathin (<50 nm) layer-by-layer (LbL) polymer multilayers. In second section, we fabricated 3D nano-canal arrays of porous alumina membranes decorated with gold nanoparticles for prospective SERS sensors. We showed extraordinary SERS enhancement and suggested that the high performance is associated with the combined effects of Raman-active hot spots of nanoparticle aggregates and the optical waveguide properties of nano-canals. We demonstrated the ability of this SERS substrate for trace level sensing of nitroaromatic explosives by detecting down to 100 zeptogram (˜330 molecules) of DNT.

  19. Effect of high saturated free fatty acids feeding on progression of renal failure in rat model of experimental nephrotoxicity.

    PubMed

    Ibraheem, Zaid O; Sattar, Munavvar A; Abdullah, Nor A; Rathore, Hassaan A; Johns, Edward J

    2012-02-01

    The current study evaluates the impact of high saturated fat feeding in rat model of experimental nephrotoxicity induced by gentamicin. Sprague-Dawley rats weighing 200 g were randomized into four groups; the first one received the standard rodents chow for 8 weeks and was treated as control, the second group (HFD)received an experimental high fat diet rich in palm kernel oil (40% of Calories as fat) for the same period. The third group (HFDG) was given 80 mg/kg (body weight)/day gentamicin sulphate intraperitoneally during the last 24 days of the feeding period while the fourth group was given gentamicin as above along with the standard rodents chow. Renal function was assessed through measuring serum creatinine, creatinine clearance and absolute and fractional excretion of both sodium and potassium. At the end, rats underwent a surgical procedure for blood pressure measurement. Renal function study showed a stronger nephrotoxicity for HFDG group. Hypertension was observed in HFD group while the pressure declined after gentamicin co-administration. Overall, changing the feeding behavior toward using more SAFFAs for rats injected with gentamicin promotes the progression of renal failure.

  20. Effect of high saturated free fatty acids feeding on progression of renal failure in rat model of experimental nephrotoxicity

    PubMed Central

    Ibraheem, Zaid O.; Sattar, Munavvar A.; Abdullah, Nor A.; Rathore, Hassaan A.; Johns, Edward J.

    2012-01-01

    The current study evaluates the impact of high saturated fat feeding in rat model of experimental nephrotoxicity induced by gentamicin. Sprague-Dawley rats weighing 200 g were randomized into four groups; the first one received the standard rodents chow for 8 weeks and was treated as control, the second group (HFD)received an experimental high fat diet rich in palm kernel oil (40% of Calories as fat) for the same period. The third group (HFDG) was given 80 mg/kg (body weight)/day gentamicin sulphate intraperitoneally during the last 24 days of the feeding period while the fourth group was given gentamicin as above along with the standard rodents chow. Renal function was assessed through measuring serum creatinine, creatinine clearance and absolute and fractional excretion of both sodium and potassium. At the end, rats underwent a surgical procedure for blood pressure measurement. Renal function study showed a stronger nephrotoxicity for HFDG group. Hypertension was observed in HFD group while the pressure declined after gentamicin co-administration. Overall, changing the feeding behavior toward using more SAFFAs for rats injected with gentamicin promotes the progression of renal failure. PMID:22364300

  1. Evaluation of the kinetic and relaxation time of gentamicin sulfate released from hybrid biomaterial Bioglass-chitosan scaffolds

    NASA Astrophysics Data System (ADS)

    Wers, E.; Oudadesse, H.; Lefeuvre, B.; Merdrignac-Conanec, O.; Barroug, A.

    2015-10-01

    Chitosan scaffolds, combined with bioactive glass 46S6, were prepared to serve as gentamicin sulfate delivery in situ systems for bone biomaterials. This work presents a study about the effect of the ratio chitosan/bioactive glass (CH/BG) on the release of gentamicin sulfate and on the bioactivity during in vitro experiments. SEM observations allowed understanding the bond between the glass grains and the chitosan matrix. In vitro results showed that scaffolds form a hydroxyapatite (HA) Ca10(PO4)6(OH)2 after 15 days of immersion in a simulated body fluid (SBF).The interest of this study is to see that the increase of the content of bioactive glass in the chitosan matrix slows the release of gentamicin sulfate in the liquid medium. Starting concentration of gentamicin sulfate has an influence on the relaxation time of the scaffolds. Indeed, an increasing concentration delays the return to a new equilibrium. Contents of chitosan and bioactive glass do not affect the relaxation time. Synthesized scaffolds could be adapted to a clinical situation: severity and type of infection, weight and age of the patient.

  2. Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

    PubMed

    Gu, Lintao; Cui, Xinhua; Wei, Wei; Yang, Jia; Li, Xuezhong

    2017-11-15

    Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Spirulina platensis protects against gentamicin-induced nephrotoxicity in rats.

    PubMed

    Karadeniz, Ali; Yildirim, Abdulkadir; Simsek, Nejdet; Kalkan, Yildiray; Celebi, Fikret

    2008-11-01

    The present study aimed to investigate the protective effect of Spirulina platensis (SP) on gentamicin sulphate (GS)-induced changes in the levels of lipid peroxidation and endogenous antioxidants in the kidney of rats. Sprague-Dawley rats were treated in separate groups as follows for 7 consecutive days: control (C), gentamicin sulphate (100 mg/kg i.p.) (GS), Spirulina platensis (1000 mg/kg orally) (SP) and Spirulina platensis (1000 mg/kg orally) plus gentamicin sulphate (100 mg/kg i.p.) (SP + GS). The degree of protection was evaluated by determining the effects of Spirulina platensis on malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX) and nitric oxide (NO), and plasma creatinine and urea levels were estimated in kidney homogenates to evaluate antioxidant activity, and the kidney was histologically examined as well. Spirulina platensis elicited significant nephroprotective activity by decreasing lipid peroxidation (MDA) and elevated the levels of GSH, SOD, GPX, NO, creatinine and urea. Furthermore, these biochemical observations were supplemented by histological examination of the rat kidneys. In conclusion, the present study indicates a very important role of reactive oxygen species (ROS) and the relation to renal dysfunction and point to the therapeutic potential of Spirulina platensis in gentamicin sulphate induced nephrotoxicity.

  4. Electrophoretic deposition of gentamicin-loaded bioactive glass/chitosan composite coatings for orthopaedic implants.

    PubMed

    Pishbin, Fatemehsadat; Mouriño, Viviana; Flor, Sabrina; Kreppel, Stefan; Salih, Vehid; Ryan, Mary P; Boccaccini, Aldo R

    2014-06-11

    Despite their widespread application, metallic orthopaedic prosthesis failure still occurs because of lack of adequate bone-bonding and the incidence of post-surgery infections. The goal of this research was to develop multifunctional composite chitosan/Bioglass coatings loaded with gentamicin antibiotic as a suitable strategy to improve the surface properties of metallic implants. Electrophoretic deposition (EPD) was applied as a single-step technology to simultaneously deposit the biopolymer, bioactive glass particles, and the antibiotic on stainless steel substrate. The microstructure and composition of the coatings were characterized using SEM/EDX, XRD, FTIR, and TGA/DSC, respectively. The in vitro bioactivity of the coatings was demonstrated by formation of hydroxyapatite after immersion in simulated body fluid (SBF) in a short period of 2 days. High-performance liquid chromatography (HPLC) measurements indicated the release of 40% of the loaded gentamicin in phosphate buffered saline (PBS) within the first 5 days. The developed composite coating supported attachment and proliferation of MG-63 cells up to 10 days. Moreover, disc diffusion test showed improved bactericidal effect of gentamicin-loaded composite coatings against S. aureus compared to control non-gentamicin-loaded coatings.

  5. Structural Analysis of the Tobramycin and Gentamicin Clinical Resistome Reveals Limitations for Next-generation Aminoglycoside Design.

    PubMed

    Bassenden, Angelia V; Rodionov, Dmitry; Shi, Kun; Berghuis, Albert M

    2016-05-20

    Widespread use and misuse of antibiotics has allowed for the selection of resistant bacteria capable of avoiding the effects of antibiotics. The primary mechanism for resistance to aminoglycosides, a broad-spectrum class of antibiotics, is through covalent enzymatic modification of the drug, waning their bactericidal effect. Tobramycin and gentamicin are two medically important aminoglycosides targeted by several different resistance factors, including aminoglycoside 2″-nucleotidyltransferase [ANT(2″)], the primary cause of aminoglycoside resistance in North America. We describe here two crystal structures of ANT(2″), each in complex with AMPCPP, Mn(2+), and either tobramycin or gentamicin. Together these structures outline ANT(2″)'s specificity for clinically used substrates. Importantly, these structures complete our structural knowledge for the set of enzymes that most frequently confer clinically observed resistance to tobramycin and gentamicin. Comparison of tobramycin and gentamicin binding to enzymes in this resistome, as well as to the intended target, the bacterial ribosome, reveals surprising diversity in observed drug-target interactions. Analysis of the diverse binding modes informs that there are limited opportunities for developing aminoglycoside analogs capable of evading resistance.

  6. Effects of Memantine on Aminoglycoside-Induced Apoptosis of Spiral Ganglion Cells in Guinea Pigs.

    PubMed

    Kim, Bo Young; Bae, Woo Yong; Hur, Dae Young; Kim, Jae-Ryong; Koh, Tae Kyung; Lee, Tae Hoon; Park, Ga Bin

    2016-07-01

    To explore whether memantine, an N-methyl-D-aspartate receptor antagonist, exerts a neuroprotective effect against apoptosis of spiral ganglion cells (SGCs) induced by gentamicin. An animal experiment. Dong-A University College of Medicine, Busan, Korea. Gentamicin was injected into the left cochleae of guinea pigs to induce apoptosis of SGCs; the contralateral cochleae served as controls. Memantine was intraperitoneally injected 12 hours and 1 hour prior to gentamicin injection. At 1 week after gentamicin and/or memantine injection, the cochleae were removed and stained with hematoxylin and eosin to evaluate morphologic changes and apoptosis. Western blotting was performed to measure FasL expression and the extent of caspase activation in SGCs. SGC numbers remained stable after memantine treatment. Western blotting showed that FasL expression and activation of caspases 3, 8, and 9 were reduced in SGCs after memantine treatment. Memantine attenuated the gentamicin-induced apoptosis of SGCs in guinea pigs. Moreover, memantine may affect Fas-FasL signaling in the receptor-mediated apoptotic pathway and caspase activation involved in the receptor-mediated and mitochondrial apoptotic pathways. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  7. 21 CFR 524.1044d - Gentamicin sulfate, betamethasone valerate ointment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... bacteria sensitive to gentamicin. (2)(i) For the treatment of acute and chronic canine otitis externa the.... The antibiotic susceptibility of the pathogenic organism should be determined prior to use of this...

  8. 21 CFR 524.1044b - Gentamicin sulfate, betamethasone valerate otic solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... use—(i) For the treatment of acute and chronic otitis externa caused by bacteria sensitive to.... (ii) For the treatment of infected superficial lesions caused by bacteria sensitive to gentamicin in...

  9. 21 CFR 524.1044b - Gentamicin sulfate, betamethasone valerate otic solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... use—(i) For the treatment of acute and chronic otitis externa caused by bacteria sensitive to.... (ii) For the treatment of infected superficial lesions caused by bacteria sensitive to gentamicin in...

  10. DNA cytoskeleton for stabilizing artificial cells.

    PubMed

    Kurokawa, Chikako; Fujiwara, Kei; Morita, Masamune; Kawamata, Ibuki; Kawagishi, Yui; Sakai, Atsushi; Murayama, Yoshihiro; Nomura, Shin-Ichiro M; Murata, Satoshi; Takinoue, Masahiro; Yanagisawa, Miho

    2017-07-11

    Cell-sized liposomes and droplets coated with lipid layers have been used as platforms for understanding live cells, constructing artificial cells, and implementing functional biomedical tools such as biosensing platforms and drug delivery systems. However, these systems are very fragile, which results from the absence of cytoskeletons in these systems. Here, we construct an artificial cytoskeleton using DNA nanostructures. The designed DNA oligomers form a Y-shaped nanostructure and connect to each other with their complementary sticky ends to form networks. To undercoat lipid membranes with this DNA network, we used cationic lipids that attract negatively charged DNA. By encapsulating the DNA into the droplets, we successfully created a DNA shell underneath the membrane. The DNA shells increased interfacial tension, elastic modulus, and shear modulus of the droplet surface, consequently stabilizing the lipid droplets. Such drastic changes in stability were detected only when the DNA shell was in the gel phase. Furthermore, we demonstrate that liposomes with the DNA gel shell are substantially tolerant against outer osmotic shock. These results clearly show the DNA gel shell is a stabilizer of the lipid membrane akin to the cytoskeleton in live cells.

  11. Highly selective electrodeposition of sub-10 nm crystalline noble metallic nanorods inside vertically aligned multiwall carbon nanotubes.

    PubMed

    Wang, Xuyang; Wang, Ranran; Wu, Qiang; Zhang, Xiaohua; Yang, Zhaohui; Guo, Jun; Chen, Muzi; Tang, Minghua; Cheng, Yajun; Chu, Haibin

    2016-07-08

    In this paper crystalline noble metallic nanorods including Au and Ag with sub-10 nm diameter, are encapsulated within prealigned and open-ended multiwall carbon nanotubes (MWCNTs) through an electrodeposition method. As the external surface of CNTs has been insulated by the epoxy the CNT channel becomes the only path for the mass transport as well as the nanoreactor for the metal deposition. Highly crystallized Au and Ag2O nanorods parallel to the radial direction of CNTs are confirmed by high-resolution transmission electron microscopy, energy dispersive x-ray spectroscopy and x-ray powder diffraction spectroscopy. The Ag2O nanorods are formed by air oxidation on the Ag metals and show a single crystalline structure with (111) planes. The Au nanorods exhibit a complex crystalline structure including twin-crystal and lattice dislocation with (111) and (200) planes. These crystalline noble metallic nanostructures may have important applications for nanocatalysts for fuel cells as well as nanoelectronic and nanophotonic devices. This method is deemed to benefit the precise deposition of other crystalline nanostructures inside CNTs with a small diameter.

  12. Highly selective electrodeposition of sub-10 nm crystalline noble metallic nanorods inside vertically aligned multiwall carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Wang, Xuyang; Wang, Ranran; Wu, Qiang; Zhang, Xiaohua; Yang, Zhaohui; Guo, Jun; Chen, Muzi; Tang, Minghua; Cheng, Yajun; Chu, Haibin

    2016-07-01

    In this paper crystalline noble metallic nanorods including Au and Ag with sub-10 nm diameter, are encapsulated within prealigned and open-ended multiwall carbon nanotubes (MWCNTs) through an electrodeposition method. As the external surface of CNTs has been insulated by the epoxy the CNT channel becomes the only path for the mass transport as well as the nanoreactor for the metal deposition. Highly crystallized Au and Ag2O nanorods parallel to the radial direction of CNTs are confirmed by high-resolution transmission electron microscopy, energy dispersive x-ray spectroscopy and x-ray powder diffraction spectroscopy. The Ag2O nanorods are formed by air oxidation on the Ag metals and show a single crystalline structure with (111) planes. The Au nanorods exhibit a complex crystalline structure including twin-crystal and lattice dislocation with (111) and (200) planes. These crystalline noble metallic nanostructures may have important applications for nanocatalysts for fuel cells as well as nanoelectronic and nanophotonic devices. This method is deemed to benefit the precise deposition of other crystalline nanostructures inside CNTs with a small diameter.

  13. Preparation of Deep Sea Fish Oil-Based Nanostructured Lipid Carriers with Enhanced Cellular Uptake.

    PubMed

    Zhu, Qiu-Yun; Guissi, Fida; Yang, Ru-Ya; Wang, Qian; Wang, Ke; Chen, Dan; Han, Zhi-Hao; Ma, Yi; Zhang, Min; Gu, Yue-Qing

    2015-12-01

    Nanostructured lipid carriers (NLC) are a promising pharmaceutical delivery system with mean diameter less than 200 nm which are dispersed in an aqueous phase containing emulsifier(s), to increase the water solubility, stability and bioavailability of oil compounds. Herein we prepared a promising NLC with glyceryl monostearate (GMS) as the solid lipid template and deep sea fish oil as the liquid lipid template using melted-ultrasonic method. Fish oil-NLC had a mean size of 84.7 ± 2.6 nm and a zeta potential that ranged from -17.87 mV to -32.91 mV. The nanoparticles exhibited good stability for four weeks with a high encapsulation efficiency of 87.5 ± 5.2%. Afterwards, confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) were used to investigate the contribution of Fish oil-NLC in enhancing fluorescein isothiocyanate (FITC) cellular uptake in comparison with free FITC. The results of this study indicated the possibility of this carrier to overcome the shortcomings of deep sea fish oil and to provide a novel bifunctional carrier with nutritional potential and drug delivery ability.

  14. Tadalafil-loaded nanostructured lipid carriers using permeation enhancers.

    PubMed

    Baek, Jong-Suep; Pham, Cuong Viet; Myung, Chang-Seon; Cho, Cheong-Weon

    2015-11-30

    Tadalafil is a phosphodiesterase-5 inhibitor indicated for the treatment of erectile dysfunction. In this study, we prepared and evaluated transdermal nanostructured lipid carriers (NLC) to improve the skin permeability of tadalafil. Tadalafil-loaded NLC dispersions were prepared using glyceryl monostearate as a solid lipid, oleic acid as a liquid lipid, and Tween 80 as a surfactant. We characterized the dispersions according to particle size, polydispersity index, zeta potential, encapsulation efficiency, and transmission electron microscopy. In vitro skin permeation studies were carried out using Franz diffusion cells, and cytotoxicity was examined using HaCaT keratinocyte cell lines. Tadalafil skin permeability increased for all tadalafil-loaded NLC formulations. The tadalafil-loaded NLC dispersion with ethanol and limonene as skin permeation enhancers exhibited the highest flux (∼4.8-fold) compared to that observed with tadalafil solution alone. Furthermore, a tadalafil-loaded NLC gel with selected permeation enhancers showed tolerance against toxicity in HaCaT cells. These results suggest that the NLC formulations with ethanol and limonene as skin permeation enhancers could be a promising dermal delivery carrier for tadalafil. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Ordered Nanostructured Amphiphile Self-Assembly Materials from Endogenous Nonionic Unsaturated Monoethanolamide Lipids in Water

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sagnella, Sharon M.; Conn, Charlotte E.; Krodkiewska, Irena

    2010-08-23

    The self-assembly, solid state and lyotropic liquid crystalline phase behavior of a series of endogenous n-acylethanolamides (NAEs) with differing degrees of unsaturation, viz., oleoyl monoethanolamide, linoleoyl monoethanolamide, and linolenoyl monoethanolamide, have been examined. The studied molecules are known to possess inherent biological function. Both the monoethanolamide headgroup and the unsaturated hydrophobe are found to be important in dictating the self-assembly behavior of these molecules. In addition, all three molecules form lyotropic liquid crystalline phases in water, including the inverse bicontinuous cubic diamond (Q{sub II}{sup D}) and gyroid (Q{sub II}{sup G}) phases. The ability of the NAE's to form inverse cubicmore » phases and to be dispersed into ordered nanostructured colloidal particles, cubosomes, in excess water, combined with their endogenous nature and natural medicinal properties, makes this new class of soft mesoporous amphiphile self-assembly materials suitable candidates for investigation in a variety of advanced multifunctional applications, including encapsulation and controlled release of therapeutic agents and incorporation of medical imaging agents.« less

  16. Live Cell Imaging of a Fluorescent Gentamicin Conjugate

    PubMed Central

    Escobedo, Jorge O.; Chu, Yu-Hsuan; Wang, Qi; Steyger, Peter S.; Strongin, Robert M.

    2012-01-01

    Understanding cellular mechanisms of ototoxic and nephrotoxic drug uptake, intracellular distribution, and molecular trafficking across cellular barrier systems aids the study of potential uptake blockers that preserve sensory and renal function during critical life-saving therapy. Herein we report the design, synthesis characterization and evaluation of a fluorescent conjugate of the aminoglycoside antibiotic gentamicin. Live cell imaging results show the potential utility of this new material. Related gentamicin conjugates studied to date quench in live kindney cells, and have been largely restricted to use in fixed (delipidated) cells. PMID:22545403

  17. Early postnatal gentamicin and ceftazidime treatment in normal and food restricted neonatal wistar rats: Implications for kidney development.

    PubMed

    Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Brüggemann, Roger J M; van den Heuvel, Lambertus P; Schreuder, Michiel F

    2017-09-01

    Up to two-thirds of premature born neonates are treated for infections with aminoglycosides such as gentamicin. Although acute toxicities are well described, there is uncertainty on developmental changes after treatment of premature born neonates. We studied the effect of gentamicin and ceftazidime on kidney development in the rat. Additionally, we evaluated the modulating effect of extrauterine growth restriction. On postnatal day (PND) 2, Wistar rats were cross-fostered into normal sized litters (12 pups) or large litters (20 pups) to create normal food (NF) or food restricted (FR) litters to simulate growth restriction and dosed daily intraperitoneally with placebo, 4 mg/kg of gentamicin or 50 mg/kg ceftazidime until PND 8. Gentamicin pharmacokinetics were studied in a separate group of animals. Kidneys were weighed. Renal expression of 18 developmental genes was evaluated by quantitative PCR on PND 8. On PND 35, glomerular number was assessed by stereology and glomerular generations were counted. Food restricted litters showed 22% less body weight compared with controls by day 35 (p < 0.001), 1.4- to 1.5-fold down regulation of Renin, Oat1, and Agtr1a (p < 0.05) expression and a 12% reduction in glomerular numbers (mean 30841 vs. 35187, p < 0.001), whereas glomerular generation count was unaffected. Gentamicin pharmacokinetic parameters were found to be in a human clinical range (mean maximum concentration in plasma of 4.88 mg/L and mean area under the plasma-concentration time curve up to the last measured concentration after 4 hr of 10.71 mg.h/L for sexes combined) and all endpoints were unaffected. Ceftazidime reduced Renin expression by 1.7-fold (p < 0.01). Our experiments showed that gentamicin at clinical levels did not disturb kidney development, ceftazidime can affect Renin expression, and extrauterine growth restriction impairs kidney development, but did not modulate potential drug toxicity. Birth Defects Research 109:1228-1235, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Disability in patients with Menière's disease following the use of two different treatment modalities: betahistine and intratympanic gentamicin.

    PubMed

    Enrique-Gonzaleza, A; Sánchez-Ferrándiz, N; Pérez-Fernández, N

    2008-01-01

    The objective of this study was to assess the level of residual disability and handicap in patients with Menière's disease (MD) that were free of new vertigo spells 2 years after having been administered treatment with either oral medication or with intratympanic gentamcin. University hospital. Tertiary medical center. 40 patients with MD were included in this study, of which 20 were treated with oral medication (betahistine) and 20 with intratympanic gentamicin; intratympanic gentamicin was for patients considered failures for the oral medication treatment. All of them are free of new vertigo in the 16-24 month period after beginning the treatment. They were matched by age and disease duration. Disability and handicap were assessed with conventional questionnaires at the time of inclusion and 2 years after beginning oral medication or ended the intratympanic gentamicin treatment. According to the treatment two groups were created: oral medication treatment and intratympanic gentamicin treatment. The amount of disability before treatment was higher in patients treated with intratympanic gentamicin than in those under oral medication; However, after treatment when no more vertigo spells takes place, this disability is significantly reduced and becomes similar for both groups of patients. In patients treated with oral medication the items reflecting the intensity of vertigo spell, the impact of vertigo in daily activities, the perception of quality of life and level of somatization do not show a significant reduction. The number or frequency of vertigo spells are very relevant for the process of disability and handicap of patients with MD when that is low or when oral medication is sufficient to eliminate vertigo spells. However when that number is high and the only possibility to arrest those vertigo spells is the use of intratympanic gentamicin, fear of vertigo must be considered as an associated problem for the patient.

  19. Detection of a Gentamicin-Resistant Burn Wound Strain of Pseudomonas Aeruginosa but Sensitive to Honey and Garcinia Kola (Heckel) Seed Extract

    PubMed Central

    Adeleke, O.E.; Coker, M.E.; Oke, O.B.

    2010-01-01

    Summary Studies on Staphylococcus aureus and Staphylococcus intermedius from dog and cat, and also on Staphylococcus aureus from wound and pyoderma infections, have shown a correlation between the site of microbial infection and antimicrobial susceptibility. Both the methanolic extract concentrate of Garcinia kola (Heckel) seeds and natural honey have been associated with activity on bacterial isolates from respiratory tract infections. In this study, selected bacteria belonging to genera from burn wound infection sites were treated with natural honey and methanolic extract concentrate of Garcinia kola in antimicrobial susceptibility tests separately and in combined form, and also with gentamicin and methanol as controls. The two natural products were found to be active on the bacterial isolates, excluding Klebsiella pneumoniae strains, all of which showed resistance to honey. Combination forms of the two natural products were active only on the strains of Pseudomonas aeruginosa. At 4 and 8 µg/ml, gentamicin was ineffective on the three strains of Klebsiella pneumoniae while 8 µg/ml was moderately active on only two strains of Pseudomonas aeruginosa. One strain of Pseudomonas aeruginosa, UCH002, was resistant to gentamicin beyond 1,000 µ/ml. Gentamicin at 4 µ/ml was inhibitory to one strain of Escherichia coli and two strains of Staphylococcus aureus. Though the antimicrobial activity of the two natural products tested had been previously reported against microbial agents of respiratory tract infection, it was also recorded in this study. The lack of activity of each of the three honey types used in this study against the Klebsiella pneumoniae strains tested underscores the need to exclude this organism from burn wound infections before embarking on treatment with honey. The sensitivity of one high-level gentamicin-resistant strain of Pseudomonas aeruginosa to honey and Garcinia kola seed extract was noteworthy considering the therapeutic failures of gentamicin and other antibiotics against Pseudomonas aeruginosa. PMID:21991206

  20. Integrated transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Com, Emmanuelle, E-mail: emmanuelle.com@univ-rennes1.fr; INSERM U625, Proteomics Core Facility Biogenouest, Rennes; Boitier, Eric

    2012-01-01

    Gentamicin is an aminoglycoside antibiotic, which induces renal tubular necrosis in rats. In the context of the European InnoMed PredTox project, transcriptomic and proteomic studies were performed to provide new insights into the molecular mechanisms of gentamicin-induced nephrotoxicity. Male Wistar rats were treated with 25 and 75 mg/kg/day subcutaneously for 1, 3 and 14 days. Histopathology observations showed mild tubular degeneration/necrosis and regeneration and moderate mononuclear cell infiltrate after long-term treatment. Transcriptomic data indicated a strong treatment-related gene expression modulation in kidney and blood cells at the high dose after 14 days of treatment, with the regulation of 463 andmore » 3241 genes, respectively. Of note, the induction of NF-kappa B pathway via the p38 MAPK cascade in the kidney, together with the activation of T-cell receptor signaling in blood cells were suggestive of inflammatory processes in relation with the recruitment of mononuclear cells in the kidney. Proteomic results showed a regulation of 163 proteins in kidney at the high dose after 14 days of treatment. These protein modulations were suggestive of a mitochondrial dysfunction with impairment of cellular energy production, induction of oxidative stress, an effect on protein biosynthesis and on cellular assembly and organization. Proteomic results also provided clues for potential nephrotoxicity biomarkers such as AGAT and PRBP4 which were strongly modulated in the kidney. Transcriptomic and proteomic data turned out to be complementary and their integration gave a more comprehensive insight into the putative mode of nephrotoxicity of gentamicin which was in accordance with histopathological findings. -- Highlights: ► Gentamicin induces renal tubular necrosis in rats. ► The mechanisms of gentamicin nephrotoxicity remain still elusive. ► Transcriptomic and proteomic analyses were performed to study this toxicity in rats. ► Transcriptomic and proteomic data turned out to be complementary and are integrated. ► A more comprehensive putative model of nephrotoxicity of gentamicin is presented.« less

  1. Irradiation-induced phenomena in carbon nanomaterials

    NASA Astrophysics Data System (ADS)

    Krasheninnikov, Arkady

    2008-03-01

    The irradiation of solids with energetic particles such as electrons or ions is associated with disorder, normally an undesirable phenomenon. However, recent experiments [for an overview, see A.V Krasheninnikov, F. Banhart, Nature Materials, 6 (2007) 723] on bombardment of carbon nanostructures with energetic particles demonstrate that irradiation can have beneficial effects and that electron or ion beams may serve as tools to change the morphology and tailor mechanical, electronic and even magnetic properties of nanostructured carbon systems. We systematically study irradiation effects in carbon nanotubes and other forms of nano-structured carbon experimentally and theoretically by employing various atomistic models ranging from empirical potentials to time-dependent density functional theory. In my presentation, I will briefly review the recent progress in our understanding of ion-irradiation-induced phenomena in nano-structured carbon and present our recent theoretical [A.V Krasheninnikov, et al., Phys. Rev. Lett., 99 (2007) 016104, A. Tolvanen et al, Appl. Phys. Lett. 91 (2007) 173109.] and experimental [O. Lehtinen et al., to be published] results. I dwell on the ``beneficial'' role of defects and impurities in nanotubes and related systems. Finally, I will present the results of simulations of irradiation-induced pressure build-up inside nanotubes encapsulated with metals [L. Sun, et al., Science 312 (2006) 1199]. Electron irradiation of such composite systems in the transmission electron microscope gives rise to contraction of nanotube shells and thus to high pressure. The irradiation-stimulated pressure can be as high as 40 GPa, which makes it possible to study phase transformations at the nanoscale with high spatial resolution. I will also address the mechanisms of plastic deformation of small metal particles inside carbon shells at high temperatures, which may be important for understanding catalytic growth of carbon nanotubes.

  2. Assessment of nutrient supplement to reduce gentamicin-induced ototoxicity.

    PubMed

    Le Prell, C G; Ojano-Dirain, C; Rudnick, E W; Nelson, M A; DeRemer, S J; Prieskorn, D M; Miller, J M

    2014-06-01

    Gentamicin is an aminoglycoside antibiotic used to treat gram-negative bacterial infections. Treatment with this antibiotic carries the potential for adverse side effects, including ototoxicity and nephrotoxicity. Ototoxic effects are at least in part a consequence of oxidative stress, and various antioxidants have been used to attenuate gentamicin-induced hair cell death and hearing loss. Here, a combination of nutrients previously shown to reduce oxidative stress in the hair cells and attenuate hearing loss after other insults was evaluated for potential protection against gentamicin-induced ototoxicity. Guinea pigs were maintained on a nutritionally complete standard laboratory animal diet or a diet supplemented with β-carotene, vitamins C and E, and magnesium. Three diets with iterative increases in nutrient levels were screened; the final diet selected for study use was one that produced statistically reliable increases in plasma levels of vitamins C and E and magnesium. In two separate studies, significant decreases in gentamicin-induced hearing loss at frequencies including 12 kHz and below were observed, with less benefit at the higher frequencies. Consistent with the functional protection, robust protection of both the inner and outer hair cell populations was observed, with protection largely in the upper half of the cochlea. Protection was independently assessed in two different laboratories, using two different strains of guinea pigs. Additional in vitro tests did not reveal any decrease in antimicrobial activity with nutrient additives. Currently, there are no FDA-approved treatments for the prevention of gentamicin-induced ototoxicity. The current data provide a rationale for continued investigations regarding translation to human patients.

  3. Do bupivacaine, clindamycin, and gentamicin at their clinical concentrations enhance rocuronium-induced neuromuscular block?

    PubMed Central

    Lee, Ji Hyeon; Park, Sang Yoong; Park, Jae-Won

    2013-01-01

    Background Bupivacaine, clindamycin, and gentamicin inhibit neuromuscular (NM) conduction. When they are combined, they may synergistically reduce the effective concentration of each to the therapeutic concentration in augmenting rocuronium-induced NM block. Thus, the aim of this study was to investigate whether combinations of the three drugs, at around their therapeutic concentrations, potentiate rocuronium-induced NM block. Methods Fifty-seven left-phrenic nerve hemidiaphragms (Male S-D rats, 150-250 g) were hung in a 20-ml organ bath filled with Krebs solution. Three consecutive single-twitch tensions (0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained. A Krebs solution was premixed with concentration sets of bupivacaine and clindamycin, bupivacaine and gentamicin, or bupivacaine, clindamycin and gentamicin. Then, the concentration of rocuronium was cumulatively increased in the Krebs solution (1, 3, 5, 7, 9, 12, 14, 16, 18, and 20 µM) until an 80% to 90% reduction in single twitch was attained. The effective concentrations for each experiment were determined with the probit model. Results The combinations of bupivacaine, clindamycin, and gentamicin enhanced rocuronium-induced NM block. When the three drugs were applied simultaneously, their concentrations were reduced to near-therapeutic levels in potentiating the action of rocuronium. Conclusions Bupivacaine, clindamycin, and gentamicin blocked NM conduction, and when all three drugs were applied together, they augmented rocuronium-induced NM block at their near-therapeutic concentrations. Clinicians should be aware of the cooperability in NM block between drugs that interrupt NM conduction. PMID:23646245

  4. Sublethal Triclosan Exposure Decreases Susceptibility to Gentamicin and Other Aminoglycosides in Listeria monocytogenes▿

    PubMed Central

    Christensen, Ellen G.; Gram, Lone; Kastbjerg, Vicky G.

    2011-01-01

    The human food-borne pathogen Listeria monocytogenes is capable of persisting in food processing plants despite cleaning and sanitation and is likely exposed to sublethal biocide concentrations. This could potentially affect susceptibility of the bacterium to biocides and other antimicrobial agents. The purpose of the present study was to determine if sublethal biocide concentrations affected antibiotic susceptibility in L. monocytogenes. Exposure of L. monocytogenes strains EGD and N53-1 to sublethal concentrations of Incimaxx DES (containing peroxy acids and hydrogen peroxide) and Triquart Super (containing quaternary ammonium compound) in four consecutive cultures did not alter the frequency of antibiotic-tolerant isolates, as determined by plating on 2× the MIC for a range of antibiotics. Exposure of eight strains of L. monocytogenes to 1 and 4 μg/ml triclosan did not alter triclosan sensitivity. However, all eight strains became resistant to gentamicin (up to 16-fold increase in MIC) after exposure to sublethal triclosan concentrations. Gentamicin-resistant isolates of strains N53-1 and 4446 were also resistant to other aminoglycosides, such as kanamycin, streptomycin, and tobramycin. Gentamicin resistance remained at a high level also after five subcultures without triclosan or gentamicin. Aminoglycoside resistance can be caused by mutations in the target site, the 16S rRNA gene. However, such mutations were not detected in the N53-1-resistant isolates. A combination of gentamicin and ampicillin is commonly used in listeriosis treatment. The triclosan-induced resistance is, hence, of great concern. Further investigations are needed to determine the molecular mechanisms underlying the effect of triclosan. PMID:21746948

  5. Hollow Silicon Nanospheres Encapsulated with a Thin Carbon Shell: An Electrochemical Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ashuri, Maziar; He, Qianran; Liu, Yuzi

    In this study we have investigated the electrochemical properties of hollow silicon nanospheres encapsulated with a thin carbon shell, HSi@C, as a potential candidate for lithium-ion battery anodes. Hollow Si nanospheres are formed using a templating method which is followed by carbon coating via carbonization of a pyrrole precursor to form HSi@C. The synthesis conditions and the resulting structure of HSi@C have been studied in detail to obtain the target design of hollow Si nanospheres encapsulated with a carbon shell. The HSi@C obtained exhibits much better electrochemical cycle stability than both micro-and nano-size silicon anodes and deliver a stable specificmore » capacity of 700 mA h g(-1) after 100 cycles at a current density of 2 A g(-1) and 800 mA h g(-1) after 120 cycles at a current density of 1 A g(-1). The superior performance of HSi@C is attributed to the synergistic combination of the nanostructured material, the enhanced conductivity, and the presence of the central void space for Si expansion with little or no change in the volume of the entire HSi@C particle. This study is the first detailed investigation of the synthesis conditions to attain the desired structure of a hollow Si core with a conductive carbon shell. This study also offers guidelines to further enhance the specific capacity of HSi@C anodes in the future.« less

  6. Hollow Silicon Nanospheres Encapsulated with a Thin Carbon Shell: An Electrochemical Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ashuri, Maziar; He, Qianran; Liu, Yuzi

    In this study we have investigated the electrochemical properties of hollow silicon nanospheres encapsulated with a thin carbon shell, HSi@C, as a potential candidate for lithium-ion battery anodes. Hollow Si nanospheres are formed using a templating method which is followed by carbon coating via carbonization of a pyrrole precursor to form HSi@C. The synthesis conditions and the resulting structure of HSi@C have been studied in detail to obtain the target design of hollow Si nanospheres encapsulated with a carbon shell. The HSi@C obtained exhibits much better electrochemical cycle stability than both micro-and nano-size silicon anodes and deliver a stable specificmore » capacity of 700 mA h g(-1) after 100 cycles at a current density of 2 A g(-1) and 800 mA h g(-1) after 120 cycles at a current density of 1 A g(-1). The superior performance of HSi@C is attributed to the synergistic combination of the nanostructured material, the enhanced conductivity, and the presence of the central void space for Si expansion with little or no change in the volume of the entire HSi@C particle. This study is the first detailed investigation of the synthesis conditions to attain the desired structure of a hollow Si core with a conductive carbon shell. This study also offers guidelines to further enhance the specific capacity of HSi@C anodes in the future. (C) 2016 Elsevier Ltd. All rights reserved.« less

  7. Microfluidics and BIO-encapsulation for drug- and cell-therapy

    NASA Astrophysics Data System (ADS)

    Aloisi, A.; Toma, C. C.; Di Corato, R.; Rinaldi, R.

    2017-08-01

    We present the construction and the application of biocompatible micro- and nano-structures that can be administered systemically and transport in a targeted and effective way drugs, small molecules, stem cells or immune system cells. These polymeric nano-systems represent a primary goal for the treatment of a wide family of neurological/systemic disorders, as well as tumors and/or acute injuries. As natural, biocompatible, biodegradable and non-immunogenic building blocks, alginate and chitosan are been currently exploited. Ionotropic pre-gelation of the alginate core, followed by chitosan polyelectrolyte complexation, allows to encapsulate selected active molecules by means of physical entrapment and electrostatic interactions within sub-micron sized hydrogel vesicles. Here we present a microfluidicassisted assembly method of nano- and micro-vesicles -under sterile, closed environment and gas exchange adjustable conditions, which is a critical issue, when the cargo to be uploaded is very sensitive. Polymer/polymer and polymer/drug mass ratio relationship are crucial in order to attain the optimum in terms of shuttle size and cargo concentration. By modulating polymer reticulation conditions, it become possible to control drug loading efficiency as well as drug delivery dynamics. Recent results on the application of these vesicles for the encapsulation and delivery of Inhibin-A and Decorin, proteins involved in acute kidney injury (AKI), for Renal tubular cell regeneration will be presented. Finally, the impact of these polysaccharide sub-micron vesicles on Human Immune cells and the metabolic and functional activity of cells embedded in the assembled vesicles will be presented and discussed.

  8. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

  9. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

  10. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

  11. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

  12. 21 CFR 522.1044 - Gentamicin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... old for treatment of porcine colibacillosis caused by strains of E. coli sensitive to gentamicin. (iii... early mortality caused by Escherichia coli. Salmonella typhimurium, and Pseudomonas aeruginosa that are... in the treatment of urinary tract infections (cystitis) caused by Proteus mirabilis, Escherichia coli...

  13. 21 CFR 522.1044 - Gentamicin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... old for treatment of porcine colibacillosis caused by strains of E. coli sensitive to gentamicin. (iii... early mortality caused by Escherichia coli. Salmonella typhimurium, and Pseudomonas aeruginosa that are... in the treatment of urinary tract infections (cystitis) caused by Proteus mirabilis, Escherichia coli...

  14. In vitro susceptibility of Prototheca spp. to gentamicin.

    PubMed Central

    Shahan, T A; Pore, R S

    1991-01-01

    One hundred strains of Prototheca zopfii, Prototheca wickerhamii, Prototheca moriformis, Prototheca stagnora, and Prototheca ulmnea; five strains of Chlorella protothecoides; and two strains of Candida albicans were obtained from a number of different clinical and environmental sources and were tested for their in vitro susceptibility to the antibacterial agent gentamicin. All Prototheca strains were susceptible to gentamicin at concentrations between 0.3 and 0.9 micrograms/ml. A modified macrobroth dilution MIC assay with a colorimeter and a microbroth dilution assay with a 96-well plate reader were the two methods used to determine the MICs. PMID:1804021

  15. One-shot, low-dosage intratympanic gentamicin for Ménière's disease: Clinical, posturographic and vestibular test findings.

    PubMed

    Daneshi, Ahmad; Jahandideh, Hesam; Pousti, Seyed Behzad; Mohammadi, Shabahang

    2014-01-01

    Ménière's disease has been remained as a difficult therapeutic challenge. The present study aimed to determine the effects of one-shot low-dosage intratympanic gentamicin on vertigo control, auditory outcomes and findings of computerized dynamic posturography and vestibular evoked myogenic potentials in patients with unilateral Ménière's disease. In a prospective clinical study, 30 patients with unilateral Ménière's disease were treated with one-shot intratympanic injection of 20 milligrams gentamicin. Main outcome measures included clinical, audiometric, postural and vestibular outcomes evaluated 1 and 9 months after the treatment. Mean vertigo attacks frequency, pure tone average threshold and functional level scale significantly decreased after the treatment (P < 0.05). Effective vertigo control (class A and B) obtained in 95.8% of the patients. In total, 75% of patients reported decrease in both aural fullness and tinnitus. Vestibular evoked myogenic potentials became absent in all the patients but four of them. Posturographic scores were improved after the treatment. One-shot low-dosage gentamicin was effective in controlling vertigo attacks in Ménière's disease and has useful effects on aural fullness and tinnitus of patients as well. Postural and vestibular tests only have adjunctive role for monitoring therapeutic responses in intratympanic gentamicin-therapy.

  16. Protective effects of hydroxytyrosol on gentamicin induced nephrotoxicity in mice.

    PubMed

    Chashmi, Nooshin Ahmadian; Emadi, Sarvenaz; Khastar, Hossein

    2017-01-22

    Gentamicin (GM) is an effective and common antibiotic against severe gram-negative infections. However, its nephrotoxic action has limited the extent of its use. The aim of this study was to investigate the protective effects of hydroxytyrosol (HT) on gentamicin induced nephrotoxicity in mice. Male mice (n = 27) were randomly assigned to three groups: (1) Sham, (2) GM (100 mg/kg for 7 days) (3) GM + HT (2 mg/kg BW; gastric gavages, for 7 days). 24-h urine samples were collected on day 8 and then animal were anesthetized. The blood and kidney tissue samples were collected. Gentamicin led to increase in plasma BUN and creatinine, fractional excretion of sodium and potassium and decrease in creatinine clearance and urine flow rate. SOD and GSH levels were reduced and MDA was increased in the GM group compared with the sham group. In GM + HT group, plasma BUN and creatinine, fractional excretion of Na, creatinine clearance and urine flow rate were decreased in contrast to GM group. Increase in SOD and GSH activity and decrease in MDA compared to GM group were seen. Findings suggest that HT partly protected the kidneys from gentamicin induced nephrotoxicity and it is partly due to antioxidant effect of HT. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Effect of gentamicin and levels of ambient sound on hearing screening outcomes in the neonatal intensive care unit: A pilot study.

    PubMed

    Garinis, Angela C; Liao, Selena; Cross, Campbell P; Galati, Johnathan; Middaugh, Jessica L; Mace, Jess C; Wood, Anna-Marie; McEvoy, Lindsey; Moneta, Lauren; Lubianski, Troy; Coopersmith, Noe; Vigo, Nicholas; Hart, Christopher; Riddle, Artur; Ettinger, Olivia; Nold, Casey; Durham, Heather; MacArthur, Carol; McEvoy, Cynthia; Steyger, Peter S

    2017-06-01

    Hearing loss rates in infants admitted to neonatal intensive care units (NICU) run at 2-15%, compared to 0.3% in full-term births. The etiology of this difference remains poorly understood. We examined whether the level of ambient sound and/or cumulative gentamicin (an aminoglycoside) exposure affect NICU hearing screening results, as either exposure can cause acquired, permanent hearing loss. We hypothesized that higher levels of ambient sound in the NICU, and/or gentamicin dosing, increase the risk of referral on the distortion product otoacoustic emission (DPOAE) assessments and/or automated auditory brainstem response (AABR) screens. This was a prospective pilot outcomes study of 82 infants (<37 weeks gestational age) admitted to the NICU at Oregon Health & Science University. An ER-200D sound pressure level dosimeter was used to collect daily sound exposure in the NICU for each neonate. Gentamicin dosing was also calculated for each infant, including the total daily dose based on body mass (mg/kg/day), as well as the total number of treatment days. DPOAE and AABR assessments were conducted prior to discharge to evaluate hearing status. Exclusion criteria included congenital infections associated with hearing loss, and congenital craniofacial or otologic abnormalities. The mean level of ambient sound was 62.9 dBA (range 51.8-70.6 dBA), greatly exceeding American Academy of Pediatrics (AAP) recommendation of <45.0 dBA. More than 80% of subjects received gentamicin treatment. The referral rate for (i) AABRs, (frequency range: ∼1000-4000 Hz), was 5%; (ii) DPOAEs with a broad F2 frequency range (2063-10031 Hz) was 39%; (iii) DPOAEs with a low-frequency F2 range (<4172 Hz) was 29%, and (iv) DPOAEs with a high-frequency F2 range (>4172 Hz) was 44%. DPOAE referrals were significantly greater for infants receiving >2 days of gentamicin dosing compared to fewer doses (p = 0.004). The effect of sound exposure and gentamicin treatment on hearing could not be determined due to the low number of NICU infants without gentamicin exposure (for control comparisons). All infants were exposed to higher levels of ambient sound that substantially exceed AAP guidelines. More referrals were generated by DPOAE assessments than with AABR screens, with significantly more DPOAE referrals with a high-frequency F2 range, consistent with sound- and/or gentamicin-induced cochlear dysfunction. Adding higher frequency DPOAE assessments to existing NICU hearing screening protocols could better identify infants at-risk for ototoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. An Antioxidant Screen Identifies Candidates for Protection of Cochlear Hair Cells from Gentamicin Toxicity

    PubMed Central

    Noack, Volker; Pak, Kwang; Jalota, Rahul; Kurabi, Arwa; Ryan, Allen F.

    2017-01-01

    Reactive oxygen species are important elements in ototoxic damage to hair cells (HCs), appearing early in the damage process. Higher levels of natural antioxidants are positively correlated with resistance to ototoxins and many studies have shown that exogenous antioxidants can protect HCs from damage. While a very wide variety of antioxidants with different characteristics and intracellular targets exist, most ototoxicity studies have focused upon one or a few well-characterized compounds. Relatively little research has attempted to determine the comparative efficacy of large variety of different antioxidants. This has been in part due to the lack of translation between cell culture and in vivo measures of efficacy. To circumvent this limitation, we used an in vitro assay based on micro-explants from the basal and middle turns of the neonatal mouse organ of Corti to screen a commercial redox library of diverse antioxidant compounds for their ability to protect mammalian HCs from a high dose of the ototoxic antibiotic gentamicin. The library included several antioxidants that have previously been studied as potential treatments for HC damage, as well as many antioxidants that have never been applied to ototoxicity. The micro-explants were treated with 200 μM gentamicin alone, gentamicin plus one of three dosages of a redox compound, the highest dosage of compound alone, or were untreated. HC counts were determined before the gentamicin insult and at 1, 2, and 3 days afterward to evaluate the HC survival. From a total of 81 antioxidant compounds, 13 exhibited significant protection of HCs. These included members of a variety of antioxidant classes with several novel antioxidants, not previously tested on HCs, appearing to alleviate the damaging gentamicin effect. Some compounds previously shown to be protective of HCs were correspondingly protective in this in vitro screen, while others were not. Finally, one of the three pro-oxidant compounds included in the library as well as six antioxidants exhibited evidence of toxicity in the absence of gentamicin. The results demonstrate the wide variability in the ability of antioxidants to protect HCs from high-dose gentamicin damage, and identify promising candidate leads for further study as potential drug targets. Highlights • A medium-throughput assay based on micro-explants of the organ of Corti was developed to screen mammalian cochlear hair cells for protection from damage by ototoxins. • Eighty one antioxidants and 3 pro-oxidants were evaluated for hair cell protection from high-dose gentamicin. • Thirteen antioxidants were significantly protective, while 6 proved to be damaging. • The use of a common assay permitted an evaluation of the relative capacity of different antioxidants for the protection of hair cells. PMID:28867994

  19. Effect of Gentamicin and Levels of Ambient Sound on Hearing Screening Outcomes in the Neonatal Intensive Care Unit: A Pilot Study

    PubMed Central

    Garinis, Angela C.; Liao, Selena; Cross, Campbell P.; Galati, Johnathan; Middaugh, Jessica L.; Mace, Jess C.; Wood, Anna-Marie; McEvoy, Lindsey; Moneta, Lauren; Lubianski, Troy; Coopersmith, Noe; Vigo, Nicholas; Hart, Christopher; Riddle, Artur; Ettinger, Olivia; Nold, Casey; Durham, Heather; MacArthur, Carol; McEvoy, Cynthia; Steyger, Peter S.

    2017-01-01

    Objective Hearing loss rates in infants admitted to neonatal intensive care units (NICU) run at 2–15%, compared to 0.3% in full-term births. The etiology of this difference remains poorly understood. We examined whether the level of ambient sound and/or cumulative gentamicin (an aminoglycoside) exposure affect NICU hearing screening results, as either exposure can cause acquired, permanent hearing loss. We hypothesized that higher levels of ambient sound in the NICU, and/or gentamicin dosing, increase the risk of referral on the distortion product otoacoustic emission (DPOAE) assessments and/or automated auditory brainstem response (AABR) screens. Methods This was a prospective pilot outcomes study of 82 infants (<37 weeks gestational age) admitted to the NICU at Oregon Health & Science University. An ER-200D sound pressure level dosimeter was used to collect daily sound exposure in the NICU for each neonate. Gentamicin dosing was also calculated for each infant, including the total daily dose based on body mass (mg/kg/day), as well as the total number of treatment days. DPOAE and AABR assessments were conducted prior to discharge to evaluate hearing status. Exclusion criteria included congenital infections associated with hearing loss, and congenital craniofacial or otologic abnormalities. Results The mean level of ambient sound was 62.9 dBA (range 51.8–70.6 dBA), greatly exceeding American Academy of Pediatrics (AAP) recommendation of <45.0 dBA. More than 80% of subjects received gentamicin treatment. The referral rate for (i) AABRs, (frequency range: ~1000–4000 Hz), was 5%; (ii) DPOAEs with a broad F2 frequency range (2063–10031 Hz) was 39%; (iii) DPOAEs with a low-frequency F2 range (<4172 Hz) was 29%, and (iv) DPOAEs with a high-frequency F2 range (>4172 Hz) was 44%. DPOAE referrals were significantly greater for infants receiving >2 days of gentamicin dosing compared to fewer doses (p= 0.004). The effect of sound exposure and gentamicin treatment on hearing could not be determined due to the low number of NICU infants without gentamicin exposure (for control comparisons). Conclusion All infants were exposed to higher levels of ambient sound that substantially exceed AAP guidelines. More referrals were generated by DPOAE assessments than with AABR screens, with significantly more DPOAE referrals with a high-frequency F2 range, consistent with sound- and/or gentamicin-induced cochlear dysfunction. Adding higher frequency DPOAE assessments to existing NICU hearing screening protocols could better identify at-risk infants to be referred for diagnostic evaluation. PMID:28483249

  20. Acute effects of gentamicin on the ionic currents of semicircular canal hair cells in the frog.

    PubMed

    Martini, Marta; Canella, Rita; Prigioni, Ivo; Russo, Giancarlo; Tavazzani, Elisa; Fesce, Riccardo; Rossi, Maria Lisa

    2011-12-01

    The effects of acute gentamicin application on hair cells isolated from the frog semicircular canals have been tested by using the patch-clamp technique in the whole-cell configuration. Extracellular gentamicin (1 mM) mostly affected the Ca(2+) macrocurrent, I(Ca), and the Ca-dependent K(+) current, I(KCa). The drug, applied to the hair cell basolateral membrane through a fast perfusion system, produced a rapid and relevant decrease (∼34%) of I(Ca) amplitude, without apparently affecting its activation-deactivation kinetics. The I(KCa) component of the delayed I(KD) was similarly affected: peak and steady-state mean amplitudes were significantly reduced, by about 47 and 54%, respectively, whereas the time constant of the mono-exponential current rising phase did not change. The Ca(2+) independent fraction of I(KD), I(KV), and the fast IA current were unaffected. Transduction channels (permeable to and blocked by gentamicin) are not available in the isolated hair cell, so the effect of intracellular gentamicin was tested by applying the drug through the patch pipette (1 mM in the pipette): again, it significantly reduced both I(Ca) and I(KD) amplitude, without affecting currents kinetics. IA properties were also unaffected. The drug did not affect the onset and removal of I(KD) inactivation, although the changes were scaled to the reduced I(KD) amplitude. From these observations, it is expected that hair cells exposed to gentamicin 'in vivo' become unresponsive to physiological stimulation (block of the transduction channels) and transmitter release at the cytoneural junction be drastically depressed due to reduced Ca(2+) inflow. In particular, functional impairment ensues much earlier than biochemical events that lead to hair cell apoptosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Nephroprotective and Anti-Inflammatory Effects of Pistacia atlantica Leaf Hydroethanolic Extract Against Gentamicin-Induced Nephrotoxicity in Rats.

    PubMed

    Heidarian, Esfandiar; Jafari-Dehkordi, Effat; Valipour, Parisa; Ghatreh-Samani, Keihan; Ashrafi-Eshkaftaki, Leila

    2017-09-03

    Gentamicin in overdose can lead to tubular injury and kidney dysfunction. Some antioxidants can protect kidneys against nephrotoxicity. This study was undertaken to evaluate the protective effects of Pistacia atlantica (P. atlantica) leaf hydroethanolic extract against gentamicin-induced nephrotoxicity in rats. Forty rats were divided into five groups: the first group received a daily intraperitoneal (i.p.) injection of normal saline. The second group received gentamicin (120 mg/kg, i.p.). The third, fourth, and fifth groups were orally treated with 200, 400, and 800 mg/kg of P. atlantica leaf hydroethanolic extract, respectively, and they also received gentamicin (120 mg/kg, i.p.). After seven days, serum malondialdehyde (MDA), creatinine (Cr), urea, uric acid, lipids profile, protein carbonyl (PC), and tumor necrosis factor-α (TNF-α) were determined. Also, a piece of kidney was used to determine catalase (CAT) and superoxide dismutase (SOD) activities, vitamin C, the gene expression of TNF-α, and for subsequent histopathological studies. Treatment with P. atlantica leaf hydroethanolic extract resulted in a significant increase (p < 0.05) in CAT, SOD, vitamin C, and high-density lipoprotein cholesterol, and significantly decreased (p < 0.05) the levels of Cr, urea, uric acid, MDA, PC, triglyceride, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, TNF-α protein, and the gene expression of TNF-α compared with the untreated group. Histopathological studies show that in lymphocyte infiltration, remarkable reduction was observed in P. atlantica leaf hydroethanolic extract-treated groups, compared with the untreated group. The present study suggests that P. atlantica leaf hydroethanolic extract has protective effects against gentamicin-induced nephrotoxicity.

  2. Selective Window Application of Gentamicin+ Dexamethasone in Meniere's Disease.

    PubMed

    Ardıç, Fazıl Necdet; Tümkaya, Funda; Aykal, Kamil; Çabuk, Burçin

    2017-08-01

    The purpose of the study is to prevent hearing loss when using intratympanic (IT) gentamicin for intractable Meniere's disease. It is a retrospective case review study. Twenty five patients who had definite Meniere's disease and had either selective window application or weekly IT gentamicin were included into the study. First group (selective) had dexamethasone on the round window and gentamicin on oval window during exploratory tympanotomy procedure. The second group had IT gentamicin at weekly intervals. The degree of caloric weakness (CW), average hearing level in low pitch (HLP) (250, 500, 1000, 2000 Hz) and high pitch (HHP) (4000, 6000, 8000 Hz) were compared before and after treatment. The need for further treatment was noted. In the first group, the average HLP was increased from 51.6±7dB to 52.2±5.6 dB. The average HHP was increased 41.96±20.2 dB to 47.2±18.3 dB after treatment. The CW changed from 37.6±23.9 % to 54.6±30.6 %. In the second group, the average HLP was increased from 56.3±10.5 dB to 61.65±18.3 dB. The average HHP was increased 59.05±17.4 dB to 69.4±21.98 dB after treatment. The CW changed from 45.8±22.3% to 71.53±29.63 %. Both methods had statisticaly significant increase in caloric weakness. But only IT gentamicin led a significant hearing loss in HHP. The use of dexamethasone and gentamycin via different windows in the middle ear is safe and effective method for Meniere's disease in the short term. Application of dexamethasone protects not only the hearing cells but vestibular cells also.

  3. Activities of fosfomycin, tigecycline, colistin, and gentamicin against extended-spectrum-β-lactamase-producing Escherichia coli in a foreign-body infection model.

    PubMed

    Corvec, Stéphane; Furustrand Tafin, Ulrika; Betrisey, Bertrand; Borens, Olivier; Trampuz, Andrej

    2013-03-01

    Limited antimicrobial agents are available for the treatment of implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli. We compared the activities of fosfomycin, tigecycline, colistin, and gentamicin (alone and in combination) against a CTX-M15-producing strain of Escherichia coli (Bj HDE-1) in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration in logarithmic phase (MBC(log)) and stationary phase (MBC(stat)) were 0.12, 0.12, and 8 μg/ml for fosfomycin, 0.25, 32, and 32 μg/ml for tigecycline, 0.25, 0.5, and 2 μg/ml for colistin, and 2, 8, and 16 μg/ml for gentamicin, respectively. In time-kill studies, colistin showed concentration-dependent activity, but regrowth occurred after 24 h. Fosfomycin demonstrated rapid bactericidal activity at the MIC, and no regrowth occurred. Synergistic activity between fosfomycin and colistin in vitro was observed, with no detectable bacterial counts after 6 h. In animal studies, fosfomycin reduced planktonic counts by 4 log(10) CFU/ml, whereas in combination with colistin, tigecycline, or gentamicin, it reduced counts by >6 log(10) CFU/ml. Fosfomycin was the only single agent which was able to eradicate E. coli biofilms (cure rate, 17% of implanted, infected cages). In combination, colistin plus tigecycline (50%) and fosfomycin plus gentamicin (42%) cured significantly more infected cages than colistin plus gentamicin (33%) or fosfomycin plus tigecycline (25%) (P < 0.05). The combination of fosfomycin plus colistin showed the highest cure rate (67%), which was significantly better than that of fosfomycin alone (P < 0.05). In conclusion, the combination of fosfomycin plus colistin is a promising treatment option for implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli.

  4. Gentamicin induces efaA expression and biofilm formation in Enterococcus faecalis.

    PubMed

    Kafil, Hossein Samadi; Mobarez, Ashraf Mohabati; Moghadam, Mehdi Forouzandeh; Hashemi, Zahra Sadat; Yousefi, Mehdi

    2016-03-01

    Enterococci have been ranked among the leading causes of nosocomial bacteremia and urinary tract infection. This study aimed to investigate the effect of ampicillin, vancomycin, gentamicin and ceftizoxime on biofilm formation and gene expression of colonization factors on Enterococcus faecalis. Twelve clinical isolates of E. faecalis were used to investigate the effect of antibiotics on biofilm formation and gene expression of efaA, asa1, ebpA, esp and ace. Flow system assay and Microtiter plates were used for biofilm assay. Two hundred clinical isolates were used for confirming the effect of antibiotics on biofilm formation. Ampicillin, vancomycin and ceftizoxime did not have any significant effect on biofilm formation, but gentamicin induced biofilm formation in 89% of isolates. In twelve selected isolate gentamicin increased expression of esp (+50.9%) and efaA (+33.9%) genes and reduced or maintained expression of others (asa1:-47.4%, ebpA: 0, ace:-19.2%). Vancomycin increased expression of esp (+89.1%) but reduced the others (asa1: -34.9%, ebpA:-11%, ace:-30%, efaA:-60%). Ceftizoxime increased slightly ebpA (+19.7%) and reduced others (asa1:-66.2%, esp:-35%, ace:-28.1%, efaA:-38.4%). and ampicillin strongly increased expression of ace (+231%), esp (+131%) and ebpA (+83%) but reduced others (asa1:-85.5%, efaA:-47.4%). The findings of the present study showed that antibiotics may have a role in biofilm formation and sustainability of enterococci, especially in case of gentamicin. efaA gene may have an important role, especially in antibiotic induced biofilm formation by gentamicin. Experiments with efaA mutants are needed to investigate the exact effect of efaA on biofilm formation with antibiotic induced cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Comparative activities of telavancin combined with nafcillin, imipenem, and gentamicin against Staphylococcus aureus.

    PubMed

    Leonard, Steven N; Supple, Megan E; Gandhi, Ronak G; Patel, Meghna D

    2013-06-01

    Beta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains of Staphylococcus aureus, 10 methicillin-susceptible S. aureus (MSSA), 10 methicillin-resistant S. aureus (MRSA), and 10 heterogeneously vancomycin-intermediate S. aureus (hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P ≤ 0.002) and were similar to each other (P ≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P ≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin against S. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.

  6. Regenerative nanomedicines: an emerging investment prospective?

    PubMed Central

    Prescott, Catherine

    2010-01-01

    Cells respond to their structural surrounding and within nanostructures exhibit unique proliferative and differentiation properties. The application of nanotechnologies to the field of regenerative medicine offers the potential to direct cell fate, target the delivery of cells and reduce immune rejection (via encapsulation), thereby supporting the development of regenerative medicines. The overall objective of any therapy is the delivery of the product not just into the clinic but also to patients on a routine basis. Such a goal typically requires a commercial vehicle and substantial levels of investment in scientific, clinical, regulatory and business expertise, resources, time and funding. Therefore, this paper focuses on some of the challenges facing this emerging industry, including investment by the venture capital community. PMID:20826478

  7. The Effects of Monitoring the Use of Gentamicin in a Community Hospital

    ERIC Educational Resources Information Center

    Gilbert, David N.; And Others

    1978-01-01

    The effect of a combined education and monitoring program on the use of gentamicin in a community hospital is described. The data support the tenet that the ways antibiotics are used can be altered by an education program. (Author/LBH)

  8. Latex agglutination inhibition card test for gentamicin assay: clinical evaluation and comparison with radioimmunoassay and bioassay.

    PubMed Central

    Standiford, H C; Bernstein, D; Nipper, H C; Caplan, E; Tatem, B; Hall, J S; Reynolds, J

    1981-01-01

    Gentamicin levels were determined in 100 serum specimens by a new latex agglutination inhibition card test, a radioimmunoassay (RIA), and a bioassay. Correlation coefficients determined by linear regression analysis demonstrated that the levels obtained by the latex agglutination inhibition card test had a high degree of correlation with the RIA and could be performed much faster and more economically when processing small numbers of specimens. The bioassay had a slightly lower degree of correlation with both the RIA and the latex test and was adversely influenced by concurrently administered antibiotics which could not be eliminated by beta-lactamase. When measuring gentamicin concentrations above 2 micrograms/ml, the coefficient of variation was less than 14% for the latex agglutination assay compared with 15% for the bioassay and 12% for RIA. The latex agglutination inhibition card test is a rapid, accurate, specific, and reproducible method for monitoring gentamicin levels in patients and is particularly applicable for laboratories processing small numbers of specimens. PMID:7247384

  9. Novel gentamicin resistance genes in Campylobacter isolated from humans and retail meats in the USA.

    PubMed

    Zhao, Shaohua; Mukherjee, Sampa; Chen, Yuansha; Li, Cong; Young, Shenia; Warren, Melissa; Abbott, Jason; Friedman, Sharon; Kabera, Claudine; Karlsson, Maria; McDermott, Patrick F

    2015-05-01

    To understand the molecular epidemiology of gentamicin-resistant Campylobacter and investigate aminoglycoside resistance mechanisms. One-hundred-and-fifty-one gentamicin-resistant Campylobacter isolates from humans (n = 38 Campylobacter jejuni; n = 41, Campylobacter coli) and retail chickens (n = 72 C. coli), were screened for the presence of gentamicin resistance genes by PCR and subtyped using PFGE. A subset of the isolates (n = 41) was analysed using WGS. Nine variants of gentamicin resistance genes were identified: aph(2″)-Ib, Ic, Ig, If, If1, If3, Ih, aac(6')-Ie/aph(2″)-Ia and aac(6')-Ie/aph(2″)-If2. The aph(2″)-Ib, Ic, If1, If3, Ih and aac(6')-Ie/aph(2″)-If2 variants were identified for the first time in Campylobacter. Human isolates showed more diverse aminoglycoside resistance genes than did retail chicken isolates, in which only aph(2″)-Ic and -Ig were identified. The aph(2″)-Ig gene was only gene shared by C. coli isolates from human (n = 27) and retail chicken (n = 69). These isolates displayed the same resistance profile and similar PFGE patterns, suggesting that contaminated retail chicken was probably the source of human C. coli infections. Human isolates were genetically diverse and generally more resistant than the retail chicken isolates. The most frequent co-resistance was to tetracycline (78/79, 98.7%), followed by ciprofloxacin/nalidixic acid (46/79, 58.2%), erythromycin and azithromycin (36/79, 45.6%), telithromycin (32/79, 40.5%) and clindamycin (18/79, 22.8%). All human and retail meat isolates were susceptible to florfenicol. This study demonstrated that several new aminoglycoside resistance genes underlie the recent emergence of gentamicin-resistant Campylobacter, and that, in addition to contaminated retail chicken, other sources have also contributed to gentamicin-resistant Campylobacter infections in humans. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. The effect of phenolic and polyphenolic compounds on the development of drug resistance.

    PubMed

    Birosová, Lucia; Mikulásová, Mária; Chromá, Magdaléna

    2005-12-01

    The effect of two phenolic compounds vanillin (4-hydroxy-3-methoxybenzaldehyde) and lignin on the development of drug/antibiotic resistance in Salmonella typhimurium was studied. Using the modified Ames test we have shown that vanillin alone has negligible effect on spontaneous mutability to ciprofloxacin and gentamicin resistance. At the tested concentrations vanillin reduces the toxicity of 4-nitroquinoline-N-oxide (4NQO) and reduces the ability of this compound to induce mutations leading to ciprofloxacin but not to gentamicin resistance. Lignin at higher concentrations increases mutagenicity to ciprofloxacin resistance and possess considerable inhibition effect on the spontaneous and 4NQO induced mutability to gentamicin resistance.

  11. Comparison of Sisomicin and Gentamicin in Bacteriuric Patients with Underlying Diseases of the Urinary Tract

    PubMed Central

    Klastersky, Jean; Hensgens, Colette; Gerard, Michel; Daneau, Didier

    1975-01-01

    Sisomicin and gentamicin (2 mg/kg) were administered in a random fashion to patients with bacteriuria superimposed on abnormalities of the urinary tract. Cure was achieved in a similar number of patients in both groups, but superinfection and reinfection with resistant microorganisms was more frequent in patients receiving gentamicin. Untoward side effects were not frequent in this series, especially if the serious underlying urological disease of most patients is taken into consideration. The susceptibility of the causative pathogens to the antibiotic administered and the severity of the underlying disease were the most important factors in the outcome. PMID:1155918

  12. 21 CFR 862.3450 - Gentamicin test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Gentamicin test system. 862.3450 Section 862.3450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862...

  13. 21 CFR 862.3450 - Gentamicin test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gentamicin test system. 862.3450 Section 862.3450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862...

  14. 21 CFR 862.3450 - Gentamicin test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Gentamicin test system. 862.3450 Section 862.3450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862...

  15. 21 CFR 862.3450 - Gentamicin test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gentamicin test system. 862.3450 Section 862.3450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862...

  16. Extended-interval Dosing of Gentamicin in Premature Neonates Born at <32 Weeks' Gestation and >7 Days of age.

    PubMed

    Sundaram, Arun; Alshaikh, Belal; Dersch-Mills, Deonne; Dobry, Jenna; Akierman, Albert R; Yusuf, Kamran

    2017-06-01

    Extended-interval dosing (EID) regimens of gentamicin have been validated for treating confirmed or suspected early- and late-onset sepsis in preterm infants in the first week of life. Despite the marked changes in volume of distribution and renal clearance in preterm infants after the first few days of life, few studies have validated EID regimens of gentamicin in this population. The objective of the study was to evaluate an EID regimen of gentamicin in infants born at <32 weeks' gestational age and aged >7 days. This observational study of an EID regimen was conducted in 39 infants. Dosing interval was based on the serum drug concentration at 22 hours after the administration of the first dose of 5 mg/kg. Gentamicin peak (5-12 µg/mL) and trough (<2 µg/mL) levels were compared to those in a historical control group of 39 infants who received traditional-interval dosing (TID) of 2.5 mg/kg of gentamicin with dosing intervals of 8, 12, or 24 hours. There were no differences in birthweight, gestational age at birth, postmenstrual age, weight at the start of gentamicin administration, postnatal age, small for gestational age status, antenatal corticosteroid use, or postnatal indomethacin exposure between the 2 groups. In the EID group, dosing intervals were 24 hours in 30 infants, 36 hours in 6 infants, and 48 hours in 3 infants. Compared with the TID group (n = 39), the EID group had a significantly higher peak level (median, 9.0 vs 4.7 µg/mL) and a significantly lower trough level (median, 0.7 vs 1.1 µg/mL) (both, P < 0.001). On regression analysis, the postmenstrual age was correlated significantly with trough levels in the EID group. There was no adverse effect on renal function in either group. On follow-up, 1 infant in the EID group and 2 infants in the TID group had evidence of sensorineural hearing loss. In infants born at <32 weeks' gestation and >7 days of age, an EID gentamicin regimen, with a dosing interval based on a single concentration measurement at 22 hours after the administration of the first dose, achieved therapeutic peak and trough levels and performed significantly better than did a TID regimen in reaching target peak and trough levels. Larger-scale trials are needed for assessing the clinical efficacy (treatment failure/success) of these regimens. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  17. Polyaniline nanowire array encapsulated in titania nanotubes as a superior electrode for supercapacitors.

    PubMed

    Xie, Keyu; Li, Jie; Lai, Yanqing; Zhang, Zhi'an; Liu, Yexiang; Zhang, Guoge; Huang, Haitao

    2011-05-01

    Conducting polymer with 1D nanostructure exhibits excellent electrochemical performances but a poor cyclability that limits its use in supercapacitors. In this work, a novel composite electrode made of polyaniline nanowire-titania nanotube array was synthesized via a simple and inexpensive electrochemical route by electropolymerizing aniline onto an anodized titania nanotube array. The specific capacitance was as high as 732 F g(-1) at 1 A g(-1), which remained at 543 F g(-1) when the current density was increased by 20 times. 74% of the maximum energy density (36.6 Wh kg(-1)) was maintained even at a high power density of 6000 W kg(-1). An excellent long cycle life of the electrode was observed with a retention of ∼86% of the initial specific capacitance after 2000 cycles. The good electrochemical performance was attributed to the unique microstructure of the electrode with disordered PANI nanowire arrays encapsulated inside the TiO(2) nanotubes, providing high surface area, fast diffusion path for ions and long-term cycle stability. Such a nanocomposite electrode is attractive for supercapacitor applications. © The Royal Society of Chemistry 2011

  18. Polymeric nanocapsules with up-converting nanocrystals cargo make ideal fluorescent bioprobes.

    PubMed

    Bazylińska, U; Wawrzyńczyk, D; Kulbacka, J; Frąckowiak, R; Cichy, B; Bednarkiewicz, A; Samoć, M; Wilk, K A

    2016-07-13

    An innovative approach for up-converting nanoparticles adaptation for bio-related and theranostic applications is presented. We have successfully encapsulated multiple, ~8 nm in size NaYF4 nanoparticles inside the polymeric nanocarriers with average size of ~150 nm. The initial coating of nanoparticles surfaces was preserved due to the hydrophobic environment inside the nanocapsules, and thus no single nanoparticle surface functionalization was necessary. The selection of biodegradable and sugar-based polyelectrolyte shells ensured biocompatibility of the nanostructures, while the choice of Tm(3+) and Yb(3+) NaYF4 nanoparticles co-doping allowed for near-infrared to near-infrared bioimaging of healthy and cancerous cell lines. The protective role of organic shell resulted in not only preserved high up-converted emission intensity and long luminescence lifetimes, without quenching from water environment, but also ensured low cytotoxicity and high cellular uptake of the engineered nanocapsules. The multifunctionality of the proposed nanocarriers is a consequence of both the organic exterior part that is accessible for conjugation with biologically important molecules, and the hydrophobic interior, which in future application may be used as a container for co-encapsulation of inorganic nanoparticles and anticancer drug cargo.

  19. Self-assembling surfactant-like peptide A6K as potential delivery system for hydrophobic drugs.

    PubMed

    Chen, Yongzhu; Tang, Chengkang; Zhang, Jie; Gong, Meng; Su, Bo; Qiu, Feng

    2015-01-01

    Finding a suitable delivery system to improve the water solubility of hydrophobic drugs is a critical challenge in the development of effective formulations. In this study, we used A6K, a self-assembling surfactant-like peptide, as a carrier to encapsulate and deliver hydrophobic pyrene. Pyrene was mixed with A6K by magnetic stirring to form a suspension. Confocal laser scanning microscopy, transmission electron microscopy, dynamic light scattering, atomic force microscopy, fluorescence, and cell uptake measurements were carried out to study the features and stability of the nanostructures, the state and content of pyrene, as well as the pyrene release profile. The suspension formed contained pyrene monomers trapped in the hydrophobic cores of the micellar nanofibers formed by A6K, as well as nanosized pyrene crystals wrapped up and stabilized by the nanofibers. The two different encapsulation methods greatly increased the concentration of pyrene in the suspension, and formation of pyrene crystals wrapped up by A6K nanofibers might be the major contributor to this effect. Furthermore, the suspension system could readily release and transfer pyrene into living cells. A6K could be further exploited as a promising delivery system for hydrophobic drugs.

  20. Nanoparticle assembled microcapsules for application as pH and ammonia sensor.

    PubMed

    Amali, Arlin Jose; Awwad, Nour H; Rana, Rohit Kumar; Patra, Digambara

    2011-12-05

    The encapsulation of molecular probes in a suitable nanostructured matrix can be exploited to alter their optical properties and robustness for fabricating efficient chemical sensors. Despite high sensitivity, simplicity, selectivity and cost effectiveness, the photo-destruction and photo-bleaching are the serious concerns while utilizing molecular probes. Herein we demonstrate that hydroxy pyrene trisulfonate (HPTS), a pH sensitive molecular probe, when encapsulated in a microcapsule structure prepared via the assembly of silica nanoparticles mediated by poly-L-lysine and trisodium citrate, provides a robust sensing material for pH sensing under the physiological conditions. The temporal evolution under continuous irradiation indicates that the fluorophore inside the silica microcapsule is extraordinarily photostable. The fluorescence intensity alternation at dual excitation facilitates for a ratiometic sensing of the pH, however, the fluorescence lifetime is insensitive to hydrogen ion concentration. The sensing scheme is found to be robust, fast and simple for the measurement of pH in the range 5.8-8.0, and can be successfully applied for the determination of ammonia in the concentration range 0-1.2 mM, which is important for aquatic life and the environment. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Polymeric nanocapsules with up-converting nanocrystals cargo make ideal fluorescent bioprobes

    PubMed Central

    Bazylińska, U.; Wawrzyńczyk, D.; Kulbacka, J.; Frąckowiak, R.; Cichy, B.; Bednarkiewicz, A.; Samoć, M.; Wilk, K. A.

    2016-01-01

    An innovative approach for up-converting nanoparticles adaptation for bio-related and theranostic applications is presented. We have successfully encapsulated multiple, ~8 nm in size NaYF4 nanoparticles inside the polymeric nanocarriers with average size of ~150 nm. The initial coating of nanoparticles surfaces was preserved due to the hydrophobic environment inside the nanocapsules, and thus no single nanoparticle surface functionalization was necessary. The selection of biodegradable and sugar-based polyelectrolyte shells ensured biocompatibility of the nanostructures, while the choice of Tm3+ and Yb3+ NaYF4 nanoparticles co-doping allowed for near-infrared to near-infrared bioimaging of healthy and cancerous cell lines. The protective role of organic shell resulted in not only preserved high up-converted emission intensity and long luminescence lifetimes, without quenching from water environment, but also ensured low cytotoxicity and high cellular uptake of the engineered nanocapsules. The multifunctionality of the proposed nanocarriers is a consequence of both the organic exterior part that is accessible for conjugation with biologically important molecules, and the hydrophobic interior, which in future application may be used as a container for co-encapsulation of inorganic nanoparticles and anticancer drug cargo. PMID:27406954

  2. Polymeric nanocapsules with up-converting nanocrystals cargo make ideal fluorescent bioprobes

    NASA Astrophysics Data System (ADS)

    Bazylińska, U.; Wawrzyńczyk, D.; Kulbacka, J.; Frąckowiak, R.; Cichy, B.; Bednarkiewicz, A.; Samoć, M.; Wilk, K. A.

    2016-07-01

    An innovative approach for up-converting nanoparticles adaptation for bio-related and theranostic applications is presented. We have successfully encapsulated multiple, ~8 nm in size NaYF4 nanoparticles inside the polymeric nanocarriers with average size of ~150 nm. The initial coating of nanoparticles surfaces was preserved due to the hydrophobic environment inside the nanocapsules, and thus no single nanoparticle surface functionalization was necessary. The selection of biodegradable and sugar-based polyelectrolyte shells ensured biocompatibility of the nanostructures, while the choice of Tm3+ and Yb3+ NaYF4 nanoparticles co-doping allowed for near-infrared to near-infrared bioimaging of healthy and cancerous cell lines. The protective role of organic shell resulted in not only preserved high up-converted emission intensity and long luminescence lifetimes, without quenching from water environment, but also ensured low cytotoxicity and high cellular uptake of the engineered nanocapsules. The multifunctionality of the proposed nanocarriers is a consequence of both the organic exterior part that is accessible for conjugation with biologically important molecules, and the hydrophobic interior, which in future application may be used as a container for co-encapsulation of inorganic nanoparticles and anticancer drug cargo.

  3. Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir System.

    PubMed

    Cho, Kwan Hyung; Jee, Jun-Pil; Yang, Da A; Kim, Sung Tae; Kang, Dongjin; Kim, Dae-Young; Sim, Taeyong; Park, Sang Yeob; Kim, Kyeongsoon; Jang, Dong-Jin

    2018-02-01

    The purpose of this study was to develop and evaluate a dry elixir (DE) system for enhancing the dissolution rate and oral bioavailability of celecoxib. DE system has been used for improving solubility, oral bioavailability of poorly water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix are rapidly dissolved due to the co-solvent effect, resting in both an enhanced dissolution and bioavailability. DEs containing celecoxib were prepared by spray-drying method and characterized by morphology, drug/ethanol content, drug crystallinity, dissolution rate and oral bioavailability. The ethanol content and drug content in DE system could be easily altered by controlling the spraydrying conditions. The dissolution profile of celecoxib from DE proved to be much higher than that of celecoxib powder due to the nano-structured matrix, amorphous state and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared with celecoxib powder alone and commercial product (Celebrex®) in rats. In particular, blood concentrations of celecoxib form DE formulation were much greater than those of native celecoxib and market product. The data demonstrate that the DE system could provide an useful solid dosage form to enhance the solubility, dissolution rate and oral bioavailability of celecoxib.

  4. Process Variables and Design of Experiments in Liposome and Nanoliposome Research.

    PubMed

    Zoghi, Alaleh; Khosravi-Darani, Kianoush; Omri, Abdelwahab

    2018-01-01

    Liposomes vesicles consisting of one or more phospholipid bilayers are microcarriers used in numerous scientific disciplines. During the last decade, nanostructured liposomes, or nanoliposomes, have been utilized in biomedical investigations due to their unique characteristics including nanoscale size, sustained release, biocompatibility, and biodegradability. The extensive literature covering the field of liposomology is an indication of increasing interests and applications in many areas, especially as carriers of active substances in nanomedicine, agriculture, food technology, and cosmetics. Nanoliposomes application as drug carriers resulted in more effective treatment of such diseases as cancers, atherosclerosis, infectious diseases and ocular disorders. In this communication, we will introduce commonly used methods for the preparation of liposome, pointing the therapeutic report of liposomes, and explaining the common process variables in liposome encapsulations. We will also review different screening methods and full and fractional factorial designs that impact independent variables in certain applications and the end-user response. We will review such key factors as encapsulation efficiency, loading capacity, particles' biologic, structural and physicochemical properties, and lipid composition in an effort to provide a comprehensive guide for liposomologists in different fields of interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Nephro-protective effect of a novel formulation of unopened coconut inflorescence sap powder on gentamicin induced renal damage by modulating oxidative stress and inflammatory markers.

    PubMed

    Jose, Svenia P; S, Asha; Im, Krishnakumar; M, Ratheesh; Santhosh, Savitha; S, Sandya; B, Girish Kumar; C, Pramod

    2017-01-01

    Fresh oyster white translucent sap obtained from the tender unopened inflorescence of coconut trees (Cocos nucifera) is identified to have great health benefits. Drug induced Nephrotoxicity is one of the major causes of renal damage in present generation. As a therapeutic agent, gentamicin imparts direct toxicity to kidney, resulting in acute tubular necrosis, glomerular and tubulointerstitial injury, haemodynamically mediated damage and obstructive nephropathy.There exists an increasing demand for safe and natural agents for the treatment and/or preventionofchronic nephrotoxicity and pathogenesis of kidney diseases. Our study shows the nephro protective/curing effect of a novel powder formulation of micronutrient enriched, unfermented coconut flower sap (CSP). The study was performed on adult male Wistar rats. The animals were grouped into three and treated separately with vehicle, gentamicin and gentamicin+CSP for 16days. Initially, gentamicin treatment significantly (p<0.05)reduced thelevels of antioxidant enzymes (SOD, CAT, GPx) and GSH and increased (p<0.05) the levels of creatinine, uric acid, urea, inflammatory markers (nitrite, IL-6, TNF- α, iNOS) and lipid peroxidation. Supplementation of coconut flower sap powder showed significant (p<0.05) reversal of all these biochemical parameters indicating an effective inhibition of the pathogenesis of nephrotoxicity and kidney disease. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. 77 FR 4226 - Oral Dosage Form New Animal Drugs; Gentamicin Sulfate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    .... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Gentamicin Sulfate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA...

  7. Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs?

    PubMed

    Das, Surajit; Ng, Wai Kiong; Tan, Reginald B H

    2012-08-30

    In recent years, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are among the popular research topics for the delivery of lipophilic drugs. Although SLNs have demonstrated several beneficial properties as drug-carrier, limited drug-loading and expulsion of drug during storage led to the development of NLCs. However, the superiority of NLCs over SLNs has not been fully established yet due to the contradictory results. In this study, SLNs and NLCs were developed using clotrimazole as model drug. Size, polydispersity index (PI), zeta potential (ZP), drug-loading (L), drug encapsulation efficiency (EE), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), drug release and stability of SLNs and NLCs were compared. Critical process parameters exhibited significant impact on the nanoparticles' properties. Size, PI, ZP and EE of the developed SLNs and NLCs were<100 nm, <0.17, <-22 mV and>82%, respectively. SEM images of SLNs and NLCs revealed spherical shaped particles (≈ 100 nm). DSC and XRD studies indicated slight difference between SLNs and NLCs as well as disappearance of the crystalline peak(s) of the encapsulated drug. NLCs demonstrated faster drug release than SLNs at low drug-loading, whereas there was no significant difference in drug release from SLNs and NLCs at high drug-loading. However, sustained/prolonged drug release was observed from both formulations. Furthermore, this study suggests that the drug release experiment should be designed considering the final application (topical/oral/parenteral) of the product. Regarding stability, NLCs showed better stability (in terms of size, PI, EE and L) than SLNs at 25°C. Moreover, there was no significant difference in drug release profile of NLCs after 3 months storage in compare to fresh NLCs, while significant change in drug release rate was observed in case of SLNs. Therefore, NLCs have an edge over SLNs. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Improved fibronectin-immobilized fibrinogen microthreads for the attachment and proliferation of fibroblasts

    PubMed Central

    Rajangam, Thanavel; An, Seong Soo A

    2013-01-01

    The aim of this study was to fabricate fibrinogen (Fbg) microfibers with different structural characteristics for the development of 3-D tissue-engineering scaffolds. Fabricated Fbg microfibers were investigated for their biomolecule encapsulation, cell adhesion, and proliferations. Microfibers with three different concentrations of Fbg (5, 10, and 15 wt%) were prepared by a gel solvent-extraction method using a silicone rubber tube. Fbg microfibers were covalently modified with fibronectin (FN) by using water-soluble 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as the cross-linking agent. Fbg microfibers were characterized by their FN cross-linking properties, structural morphology, and in vitro degradation. Furthermore, FN/Fbg microfibers were evaluated for cell attachment and proliferation. The bio-compatibility and cell proliferation of the microfibers were assessed by measuring adenosine triphosphate activity in C2C12 fibroblast cells. Cell attachment and proliferation on microfibers were further examined using fluorescence and scanning electron microscopic images. FN loading on the microfibers was confirmed by fluorescence and infrared spectroscopy. Surface morphology was characterized by scanning electron microscopy, and showed highly aligned nanostructures for fibers made with 15 wt% Fbg, a more porous structure for fibers made with 10 wt% Fbg, and a less porous structure for those made with 5 wt% Fbg. Controlled biodegradation of the fiber was observed for 8 weeks by using an in vitro proteolytic degradation assay. Fbg microfibers with highly aligned nanostructures (15 wt%) showed enhanced biomolecule encapsulation, as well as higher cell adhesion and proliferation than another two types of FN/Fbg fibers (5 and 10 wt%) and unmodified Fbg fibers. The promising results obtained from the present study reveal that optimal structure of Fbg microfibers could be used as a potential substratum for growth factors or drug release, especially in wound healing and vascular tissue engineering, in which fibers could be applied to promote and orient cell adhesion and proliferation. PMID:23515334

  9. Low temperature surface chemistry and nanostructures

    NASA Astrophysics Data System (ADS)

    Sergeev, G. B.; Shabatina, T. I.

    2002-03-01

    The new scientific field of low temperature surface chemistry, which combines the low temperature chemistry (cryochemistry) and surface chemistry approaches, is reviewed in this paper. One of the most exciting achievements in this field of science is the development of methods to create highly ordered hybrid nanosized structures on different organic and inorganic surfaces and to encapsulate nanosized metal particles in organic and polymer matrices. We consider physical and chemical behaviour for the systems obtained by co-condensation of the components vapours on the surfaces cooled down to 4-10 and 70-100 K. In particular the size effect of both types, the number of atoms in the reactive species structure and the thickness of growing co-condensate film, on the chemical activity of the system is analysed in detail. The effect of the internal mechanical stresses on the growing interfacial co-condensate film formation and on the generation of fast (explosive) spontaneous reactions at low temperatures is discussed. The examples of unusual chemical interactions of metal atoms, clusters and nanosized particles, obtained in co-condensate films on the cooled surfaces under different conditions, are presented. The examples of highly ordered surface and volume hybrid nanostructures formation are analysed.

  10. Design and realization of transparent solar modules based on luminescent solar concentrators integrating nanostructured photonic crystals.

    PubMed

    Jiménez-Solano, Alberto; Delgado-Sánchez, José-Maria; Calvo, Mauricio E; Miranda-Muñoz, José M; Lozano, Gabriel; Sancho, Diego; Sánchez-Cortezón, Emilio; Míguez, Hernán

    2015-12-01

    Herein, we present a prototype of a photovoltaic module that combines a luminescent solar concentrator integrating one-dimensional photonic crystals and in-plane CuInGaSe 2 (CIGS) solar cells. Highly uniform and wide-area nanostructured multilayers with photonic crystal properties were deposited by a cost-efficient and scalable liquid processing amenable to large-scale fabrication. Their role is to both maximize light absorption in the targeted spectral range, determined by the fluorophore employed, and minimize losses caused by emission at angles within the escape cone of the planar concentrator. From a structural perspective, the porous nature of the layers facilitates the integration with the thermoplastic polymers typically used to encapsulate and seal these modules. Judicious design of the module geometry, as well as of the optical properties of the dielectric mirrors employed, allows optimizing light guiding and hence photovoltaic performance while preserving a great deal of transparency. Optimized in-plane designs like the one herein proposed are of relevance for building integrated photovoltaics, as ease of fabrication, long-term stability and improved performance are simultaneously achieved. © 2015 The Authors. Progress in Photovoltaics: Research and Applications published by John Wiley & Sons Ltd.

  11. Design and realization of transparent solar modules based on luminescent solar concentrators integrating nanostructured photonic crystals

    PubMed Central

    Jiménez‐Solano, Alberto; Delgado‐Sánchez, José‐Maria; Calvo, Mauricio E.; Miranda‐Muñoz, José M.; Lozano, Gabriel; Sancho, Diego; Sánchez‐Cortezón, Emilio

    2015-01-01

    Abstract Herein, we present a prototype of a photovoltaic module that combines a luminescent solar concentrator integrating one‐dimensional photonic crystals and in‐plane CuInGaSe2 (CIGS) solar cells. Highly uniform and wide‐area nanostructured multilayers with photonic crystal properties were deposited by a cost‐efficient and scalable liquid processing amenable to large‐scale fabrication. Their role is to both maximize light absorption in the targeted spectral range, determined by the fluorophore employed, and minimize losses caused by emission at angles within the escape cone of the planar concentrator. From a structural perspective, the porous nature of the layers facilitates the integration with the thermoplastic polymers typically used to encapsulate and seal these modules. Judicious design of the module geometry, as well as of the optical properties of the dielectric mirrors employed, allows optimizing light guiding and hence photovoltaic performance while preserving a great deal of transparency. Optimized in‐plane designs like the one herein proposed are of relevance for building integrated photovoltaics, as ease of fabrication, long‐term stability and improved performance are simultaneously achieved. © 2015 The Authors. Progress in Photovoltaics: Research and Applications published by John Wiley & Sons Ltd. PMID:27656090

  12. Cd-free Cu-Zn-In-S/ZnS quantum dots@SiO2 multiple cores nanostructure: preparation and application for white LEDs

    NASA Astrophysics Data System (ADS)

    Jiang, Tongtong; Shen, Mohan; Dai, Peng; Wu, Mingzai; Yu, Xinxin; Li, Guang; Xu, Xiaoliang; Zeng, Haibo

    2017-10-01

    The work reports the fabrication of Cu doped Zn-In-S (CZIS) alloy quantum dots (QDs) using dodecanethiol and oleic acid as stabilizing ligands. With the increase of doped Cu element, the photoluminescence (PL) peak is monotonically red shifted. After coating ZnS shell, the PL quantum yield of CZIS QDs can reach 78%. Using reverse micelle microemulsion method, CZIS/ZnS QDs@SiO2 multi-core nanospheres were synthesized to improve the colloidal stability and avoid the aggregation of QDs. The obtained multi-core nanospheres were dispersed in curing adhesive, and applied as a color conversion layer in down converted light-emitting diodes. After encapsulation in curing adhesive, the newly designed LEDs show artifically regulated color coordinates with varying the weight ratio of green QDs and red QDs, and the concentrations of these two types of QDs. Moreover, natural white and warm white LEDs with correlated color temperature of 5287, 6732, 2731, and 3309 K can be achieved, which indicates that CZIS/ZnS QDs@SiO2 nanostructures are promising color conversion layer material for solid-state lighting application.

  13. Hydrophobization of Concrete Using Granular Nanostructured Aggregate

    NASA Astrophysics Data System (ADS)

    Ogurtsova, Y. N.; Strokova, V. V.; Labuzova, M. V.

    2017-11-01

    The possibility of giving hydrophobical properties to the fine-grained concrete matrix by using a granular nanostructured aggregate (GNA) with a hydrophobizing additive is investigated in this work. GNA is obtained by granulating the silica raw material with an alkaline component. The introduction of a hydrophobizing additive into the raw mix of GNA allows to encapsulate it reducing the negative effect on hydration processes, the intensity of migration of moisture and efflorescence in concrete and, consequently, improving the performance characteristics of fine-grained concrete products. The hydrophobizing ability of a solution of sodium polysilicates formed in the core of GNA during concrete heat and moisture treatment is proved. The analysis of IR spectra after the impregnation of cement stone samples with a solution of sodium polysilicates showed an increase in the degree of hydration and the formation of framework water aluminosilicates. Atmospheric processes modelling showed that the use of GNA on the basis of gaize with calcium stearate and on the basis of fly ash with GKZh-11 makes it possible to increase the resistance of fine-grained concrete to the atmospheric effect of the medium, namely, the outwashing of readily soluble compounds.

  14. Self-assembly of coiled coil peptides into nanoparticles vs 2-d plates: effects of assembly pathway

    NASA Astrophysics Data System (ADS)

    Kim, Kyunghee; Pochan, Darrin

    Molecular solution assembly, or self-assembly, is a process by which ordered nanostructures or patterns are formed by non-covalent interactions during assembly. Biomimicry, the use of bioinspired molecules or biologically relevant materials, is an important area of self-assembly research with peptides serving a critical role as molecular tools. The morphology of peptide assemblies can be controlled by adjusting solution conditions such as the concentration of peptides, the temperature, and pH. Herein, spherical nanostructures, which have potential for creating an encapsulation system, are formed by self-assembly when coiled coil peptides are combined in solution. These peptides are homotrimeric and heterodimeric coiled-coil bundles and the homotrimer is connected with each of heterodimer through their external surfaces via disulfide bonds. The resultant covalent constructs could co-assemble into complementary trimeric hubs, respectively. The two peptide constructs are directly mixed and assembled in solution in order to produce either spherical particles or 2-d plates depending on the solution conditions and kinetic pathway of assembly. In particular, structural changes of the self-assembled peptides are explored by control of the thermal history of the assembly solution.

  15. Sulfur cathodes with hydrogen reduced titanium dioxide inverse opal structure.

    PubMed

    Liang, Zheng; Zheng, Guangyuan; Li, Weiyang; Seh, Zhi Wei; Yao, Hongbin; Yan, Kai; Kong, Desheng; Cui, Yi

    2014-05-27

    Sulfur is a cathode material for lithium-ion batteries with a high specific capacity of 1675 mAh/g. The rapid capacity fading, however, presents a significant challenge for the practical application of sulfur cathodes. Two major approaches that have been developed to improve the sulfur cathode performance include (a) fabricating nanostructured conductive matrix to physically encapsulate sulfur and (b) engineering chemical modification to enhance binding with polysulfides and, thus, to reduce their dissolution. Here, we report a three-dimensional (3D) electrode structure to achieve both sulfur physical encapsulation and polysulfides binding simultaneously. The electrode is based on hydrogen reduced TiO2 with an inverse opal structure that is highly conductive and robust toward electrochemical cycling. The relatively enclosed 3D structure provides an ideal architecture for sulfur and polysulfides confinement. The openings at the top surface allow sulfur infusion into the inverse opal structure. In addition, chemical tuning of the TiO2 composition through hydrogen reduction was shown to enhance the specific capacity and cyclability of the cathode. With such TiO2 encapsulated sulfur structure, the sulfur cathode could deliver a high specific capacity of ∼1100 mAh/g in the beginning, with a reversible capacity of ∼890 mAh/g after 200 cycles of charge/discharge at a C/5 rate. The Coulombic efficiency was also maintained at around 99.5% during cycling. The results showed that inverse opal structure of hydrogen reduced TiO2 represents an effective strategy in improving lithium sulfur batteries performance.

  16. 21 CFR 520.1044a - Gentamicin sulfate oral solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate oral solution. 520.1044a Section 520.1044a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1044a...

  17. Protective effect of the methanolic leaf extract of Eclipta alba (L.) Hassk. (Asteraceae) against gentamicin-induced nephrotoxicity in Sprague Dawley rats.

    PubMed

    Dungca, Niña Theresa P

    2016-05-26

    Eclipta alba, also known as Eclipta prostrata, is a weed of the family Asteraceae found in tropical and subtropical regions widely used in herbal medicine, including treatment of renal diseases. This study aims to evaluate the protective effect of the methanolic leaf extract of Eclipta alba on gentamicin-induced nephrotoxicity in rats. Nephrotoxicity was induced in rats by subcutaneous injection of gentamicin (80mg/kg/day for seven days). Quercetin was used as a positive control. The nephroprotective activity was evaluated by determining blood urea nitrogen, serum creatinine, urinary microprotein, renal catalase and malondialdehyde levels. The extract protected the rat kidneys against gentamicin-induced renal tubular alterations and rises in blood urea nitrogen, serum creatinine, and microprotein levels. Lipid peroxidation and decrement in catalase levels were also ameliorated. The study revealed the protective effect of the methanolic leaf extract of E. alba and suggests that the probable mechanism for the nephroprotection by the extract may be due to its good radical scavenging activity and Fe(3+) ion-reducing ability. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Gentamicin: effect on E. coli in space

    NASA Technical Reports Server (NTRS)

    Kacena, M. A.; Todd, P.

    1999-01-01

    Previous investigations have shown that liquid bacterial cultures grown in space flight were not killed as effectively by antibiotic treatments as were cultures grown on Earth. However, the cause for the decreased antibiotic effectiveness remains unknown. Possible explanations include modified cell proliferation and modified antibiotic transport in the culture medium. Escherichia coli cultures were grown in space flight (STS-69 and STS-73), with and without gentamicin, on a solid agar substrate thus eliminating fluid effects and reducing the unknowns associated with space-flight bacterial cultures in suspension. This research showed that E. coli cultures grown in flight on agar for 24 to 27 hours experienced a heightened growth compared to simultaneous controls. However, addition of gentamicin to the agar killed the bacteria such that both flight and ground control E. coli samples had similar final cell concentrations. Therefore, while the reported existence of a decrease in antibiotic effectiveness in liquid cultures remains unexplained, these data suggest that gentamicin in space flight was at least as effective as, if not more effective than, on Earth, when E. coli cells were grown on agar.

  19. Mechanisms of the post-antibiotic effects induced by rifampicin and gentamicin in Escherichia coli.

    PubMed

    Stubbings, William; Bostock, Julieanne; Ingham, Eileen; Chopra, Ian

    2006-08-01

    The mechanisms by which antibiotics induce a post-antibiotic effect in susceptible bacteria are poorly understood. To explore the mechanisms more fully we examined the recovery of macromolecular synthesis in Escherichia coli during gentamicin- and rifampicin-induced post-antibiotic effects. E. coli ATCC 25922 was exposed to rifampicin and to gentamicin at 5x MIC for 60 min to induce post-antibiotic effects. The antibiotics were then removed from the culture medium by washing the cells. The rates of DNA, RNA and protein synthesis during the post-antibiotic effect and recovery periods were subsequently determined by measuring the incorporation of radiolabelled uridine, thymidine and leucine into trichloroacetic acid precipitable material. Recovery of E. coli ATCC 25922 from the rifampicin-induced post-antibiotic effect coincided with the recovery of RNA and protein synthesis. Recovery from the gentamicin-induced post-antibiotic effect coincided with the recovery of protein synthesis. These data support the hypothesis that antibiotic molecules retained in the cell mediate the post-antibiotic effect by suppressing the biochemical activity of their molecular targets.

  20. In vitro assessment of nanosilver-functionalized PMMA bone cement on primary human mesenchymal stem cells and osteoblasts.

    PubMed

    Pauksch, Linda; Hartmann, Sonja; Szalay, Gabor; Alt, Volker; Lips, Katrin S

    2014-01-01

    Peri-prosthetic infections caused by multidrug resistant bacteria have become a serious problem in surgery and orthopedics. The aim is to introduce biomaterials that avoid implant-related infections caused by multiresistant bacteria. The efficacy of silver nanoparticles (AgNP) against a broad spectrum of bacteria and against multiresistant pathogens has been repeatedly described. In the present study polymethylmethacrylate (PMMA) bone cement functionalized with AgNP and/or gentamicin were tested regarding their biocompatibility with bone forming cells. Therefore, influences on viability, cell number and differentiation of primary human mesenchymal stem cells (MSCs) and MSCs cultured in osteogenic differentiation media (MSC-OM) caused by the implant materials were studied. Furthermore, the growth behavior and the morphology of the cells on the testing material were observed. Finally, we examined the induction of cell stress, regarding antioxidative defense and endoplasmatic reticulum stress. We demonstrated similar cytocompatibility of PMMA loaded with AgNP compared to plain PMMA or PMMA loaded with gentamicin. There was no decrease in cell number, viability and osteogenic differentiation and no induction of cell stress for all three PMMA variants after 21 days. Addition of gentamicin to AgNP-loaded PMMA led to a slight decrease in osteogenic differentiation. Also an increase in cell stress was detectable for PMMA loaded with gentamicin and AgNP. In conclusion, supplementation of PMMA bone cement with gentamicin, AgNP, and both results in bone implants with an antibacterial potency and suitable cytocompatibility in MSCs and MSC-OM.

  1. [Lack of protection against gentamicin ototoxicity by auditory conditioning with noise].

    PubMed

    Strose, Alex; Hyppolito, Miguel Ângelo; Colombari, Gleice Cristina; Rossato, Maria; Oliveira, Jose Antônio Aparecido de

    2014-01-01

    Auditory conditioning consists of the pre-exposure to low levels of a potential harmful agent to protect against a subsequent harmful exposure. To confirm if conditioning with an agent different from that used to cause the trauma can also be effective. This was an experimental study with 17 guinea pigs, divided into three groups: an ototoxic control group (Cont) that received intramuscular administration of gentamicin 160 mg/kg/day for ten consecutive days, but no sound exposure; a sound control group (Sound) that was exposed to 85 dB broadband noise centered at 4 kHz, 30 min each day for ten consecutive days, but received no ototoxic medications; and an experimental group (Expt) that received sound exposure identical to the Sound group and after each noise presentation, received gentamicin similarly to Cont group. The animals were evaluated by distortion product otoacoustic emissions (DPOAEs), brainstem auditory evoked potentials (BAEPs), and scanning electron microscopy. The animals that were conditioned with noise did not show any protective effect compared with the ones that received only the ototoxic gentamicin administration. This lack of protection was observed functionally and morphologically. Conditioning with 85 dB broadband noises, 30 min a day for ten consecutive days does not protect against an ototoxic gentamicin administration of 160 mg/kg/day for ten consecutive days in the guinea pig. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  2. Spherical gold nanoparticles and gold nanorods for the determination of gentamicin

    NASA Astrophysics Data System (ADS)

    Miranda-Andrades, Jarol R.; Pérez-Gramatges, Aurora; Pandoli, Omar; Romani, Eric C.; Aucélio, Ricardo Q.; da Silva, Andrea R.

    2017-02-01

    Gentamicin is an antibiotic indicated to treat mastitis in dairy cattle and for the treatment of bacterial resistance in the context of hospital infections. The effect caused by gentamicin on the optical properties of gold nanoparticles aqueous dispersions were used to develop quantitative methods to determine this antibiotic. Two different aqueous dispersions, one containing spherical Au nanoparticles (AuNPs) and the other containing Au nanorods (AuNRs), had their conditions adjusted to enable a stable and sensitive response towards gentamicin. The use of AuNPs, with measurement at 681 nm of the rising coupling plasmon band, enabled a limit of detection (LOD) of 0.4 ng mL- 1 (0.02 ng absolute LOD), ten times lower than the one achieved by measuring the decreasing of the longitudinal surface plasmon resonance band (at 662 nm). The linear analytical response of AuNPs measured at 681 nm did not require rationing of signal values to correct for linearity. Stability of the analytical response resulted in intermediary precision below 2%. No significant interference was imposed by excipients traditionally present in injectable solutions for veterinary use. Percent recoveries obtained in such formulations were between 94.5 and 98.2% regardless the existence of any difference in the proportion of the compounds known as gentamicin (C1, C1a and C2) in standard and in the samples. The method requires no derivatization with toxic reagents as usually is required in other spectroscopic approaches.

  3. Synthesis and characterization of a novel controlled release zinc oxide/gentamicin-chitosan composite with potential applications in wounds care.

    PubMed

    Vasile, Bogdan Stefan; Oprea, Ovidiu; Voicu, Georgeta; Ficai, Anton; Andronescu, Ecaterina; Teodorescu, Andrei; Holban, Alina

    2014-03-25

    Freshly prepared ZnO nanoparticles were incorporated into a chitosan solution in weight ratios ranging from 1:1 to 12:1. Starting from the ratio of 3:1 the chitosan solution was transformed into a gel with a high consistency, which incorporates 15mL water for only 0.1g solid substance. The powders obtained after drying the gel were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and thermal analysis (TG-DSC). The electronic (UV-vis), infrared (FTIR) and photoluminescence (PL) spectra were also recorded. ZnO particles were coated with gentamicin and incorporated into the chitosan matrix, to yield a ZnO/gentamicin-chitosan gel. The release rate of gentamicin was monitored photometrically. This ZnO/gentamicin-chitosan gel proved great antimicrobial properties, inhibiting Staphylococcus aureus and Pseudomonas aeruginosa growth in both planktonic and surface-attached conditions. The results indicate that the obtained composite can be used in cutaneous healing for developing improved wound dressings, which combine the antibacterial activity of all three components with the controlled release of the antibiotic. This wound dressing maintains a moist environment at the wound interface, providing a cooling sensation and soothing effect, while slowly releasing the antibiotic. The system is fully scalable to any other soluble drug, as the entire solution remains trapped in the ZnO-chitosan gel. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Preclinical and Clinical Studies of Unrelieved Aural Fullness following Intratympanic Gentamicin Injection in Patients with Intractable Ménière’s Disease

    PubMed Central

    Zhai, Feng; Zhang, Ru; Zhang, Ting; Steyger, Peter S.; Dai, Chun-Fu

    2014-01-01

    Objective To clarify whether gentamicin affects vestibular dark cells in guinea pigs and relieves patients of aural fullness with intractable Ménière’s disease following intratympanic administration. Materials and Methods Purified gentamicin-Texas Red (GTTR) was injected intratympanically in guinea pigs that were sacrificed at 1, 3, 7, 14 and 28 days. GTTR uptake was examined in hair cells, and transitional cells and dark cells in vestibular end-organs were examined. Specific attention was paid to its distribution in dark cells under confocal microscopy, and the ultrastructure of dark cells using electron microscopy, following intratympanic injection. Results Dark cells in the semicircular canals showed weak GTTR uptake at 1, 3, 7, 14 and 28 days after intratympanic injection, with no significant differences at various time points after injection. However, the adjacent transitional cells demonstrated intense GTTR uptake that was retained for at least 28 days. Ultrastructural studies demonstrated negligible characteristics associated with apoptosis or necrosis in these dark cells. The tight junctions between dark cells showed no signs of disruption at 7 or 28 days after injection. Conclusion Intratympanic gentamicin has little direct impact on vestibular dark cells. Clinical Application A modified low-dose titration intratympanic approach was used in 29 patients with intractable vertigo and the clinical outcomes were followed. Aural fullness following intratympanic gentamicin injection was not relieved based on our subjective scales, demonstrated by no statistically significant difference between preinjection (4.16 ± 3.08) and postinjection (3.58 ± 2.93; p > 0.05) aural fullness scores. Vertigo control was achieved in 88% of patients, with hearing deterioration identified in 16% of patients. Intratympanic gentamicin administration might not lead to relief of aural fullness in patients with intractable vertigo, although it can achieve a high vertigo control rate with some cochleotoxicity. PMID:24008307

  5. Extended-Interval Gentamicin Dosing in Achieving Therapeutic Concentrations in Malaysian Neonates

    PubMed Central

    Tan, Sin Li; Wan, Angeline SL

    2015-01-01

    OBJECTIVE: To evaluate the usefulness of extended-interval gentamicin dosing practiced in neonatal intensive care unit (NICU) and special care nursery (SCN) of a Malaysian hospital. METHODS: Cross-sectional observational study with pharmacokinetic analysis of all patients aged ≤28 days who received gentamicin treatment in NICU/SCN. Subjects received dosing according to a regimen modified from an Australian-based pediatric guideline. During a study period of 3 months, subjects were evaluated for gestational age, body weight, serum creatinine concentration, gentamicin dose/interval, serum peak and trough concentrations, and pharmacokinetic parameters. Descriptive percentages were used to determine the overall dosing accuracy, while analysis of variance (ANOVA) was conducted to compare the accuracy rates among different gestational ages. Pharmacokinetic profile among different gestational age and body weight groups were compared by using ANOVA. RESULTS: Of the 113 subjects included, 82.3% (n = 93) achieved therapeutic concentrations at the first drug-monitoring assessment. There was no significant difference found between the percentage of term neonates who achieved therapeutic concentrations and the premature group (87.1% vs. 74.4%), p = 0.085. A total of 112 subjects (99.1%) achieved desired therapeutic trough concentration of <2 mg/L. Mean gentamicin peak concentration was 8.52 mg/L (95% confidence interval [Cl], 8.13–8.90 mg/L) and trough concentration was 0.54 mg/L (95% CI, 0.48–0.60 mg/L). Mean volume of distribution, half-life, and elimination rate were 0.65 L/kg (95% CI, 0.62–0.68 L/kg), 6.96 hours (95% CI, 6.52–7.40 hours), and 0.11 hour−1 (95% CI, 0.10–0.11 hour−1), respectively. CONCLUSION: The larger percentage of subjects attaining therapeutic range with extended-interval gentamicin dosing suggests that this regimen is appropriate and can be safely used among Malaysian neonates. PMID:25964729

  6. Hair cell regeneration or the expression of related factors that regulate the fate specification of supporting cells in the cochlear ducts of embryonic and posthatch chickens.

    PubMed

    Jiang, Lingling; Jin, Ran; Xu, Jincao; Ji, Yubin; Zhang, Meiguang; Zhang, Xuebo; Zhang, Xinwen; Han, Zhongming; Zeng, Shaoju

    2016-02-01

    Hair cells in posthatch chickens regenerate spontaneously through mitosis or the transdifferentiation of supporting cells in response to antibiotic injury. However, how embryonic chicken cochleae respond to antibiotic treatment remains unknown. This study is the first to indicate that unlike hair cells in posthatch chickens, the auditory epithelium was free from antibiotic injury (25-250 mg gentamicin/kg) in embryonic chickens, although FITC-conjugated gentamicin actually reached embryonic hair cells. Next, we examined and counted the cells and performed labeling for BrdU, Sox2, Atoh1/Math1, PV or p27(kip1) (triple or double labeling) in the injured cochlea ducts after gentamicin treatment at 2 h (h), 15 h, 24 h, 2 days (d), 3 d and 7 d after BrdU treatment in posthatch chickens. Our results indicated that following gentamicin administration, proliferating cells (BrdU+) were labeled for Atoh1/Math1 in the damaged areas 3d after gentamicin administration, whereas hair cells (PV+) renewed through mitosis (BrdU+) or direct transdifferentiation (BrdU-) were evident only after 5 d of gentamicin administration. In addition, Sox2 expression was up-regulated in triggered supporting cells at an early stage of regeneration, but stopped at the advent of mature hair cells. Our study also indicated that p27(kip1) was expressed in both hair cells and supporting cells but was down-regulated in a subgroup of the supporting cells that gave rise to hair cells. These data and the obtained dynamic changes of the cells labeled for BrdU, Sox2, Atoh1/Math1, PV or p27(kip1) are useful for understanding supporting cell behaviors and their fate specification during hair cell regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Genotypic characterization of gentamicin and cephalosporin resistant Escherichia coli isolates from blood cultures in a Norwegian university hospital 2011-2015.

    PubMed

    Fladberg, Øyvind Andreas; Jørgensen, Silje Bakken; Aamot, Hege Vangstein

    2017-01-01

    Cephalosporin resistance in clinical E. coli isolates is increasing internationally. The increase has been caused by virulent and often multidrug-resistant clones, especially the extended spectrum β-lactamase (ESBL) producing E. coli clone O25b-ST131. In Norway, recommended empirical treatment of sepsis consists of gentamicin and penicillin combined, or a broad-spectrum cephalosporin. To investigate if increased gentamicin and cephalosporins resistance rates in our hospital could be caused by specific clones, we conducted a retrospective study on E. coli blood culture isolates from 2011 through 2015. All E. coli isolates non-susceptible to gentamicin and/or third-generation cephalosporins were genotyped using multiple-locus variable-number of tandem repeat analysis (MLVA) and compared with antibiotic susceptible isolates. The frequency of the most common genes causing ESBL production ( bla CTX-M , bla ampC ) was examined by Real-Time PCR. A total of 158 cephalosporin and/or gentamicin resistant and 97 control isolates were differentiated into 126 unique MLVA types. Of these, 31% of the isolates belonged to a major MLVA cluster consisting of 41% of the gentamicin resistant and 35% of the cephalosporin resistant isolates. The majority (65/80 isolates) of this MLVA cluster contained MLVA types associated with the E. coli O25b-ST131 clone. Genes encoding CTX-M enzyme phylogroups 1 and 9 occurred in 65% and 19% of cephalosporin resistant isolates, respectively, whereas bla ampC-CIT was identified in 3%. No local E. coli bacteraemia clone was identified. Antibiotic resistance was dispersed over a variety of genotypes. However, association with the international E. coli O25b-ST131 clone was frequent and may be an important driver behind increased resistance rates. Monitoring and preventing dissemination of these resistant clones are important for continued optimal treatment.

  8. Multiwall carbon nanotubes chemically modified carbon paste electrodes for determination of gentamicin sulfate in pharmaceutical preparations and biological fluids.

    PubMed

    Khalil, M M; Abed El-Aziz, G M

    2016-02-01

    This article focused on the construction and characteristics of novel and sensitive gentamicin carbon paste electrodes which are based on the incorporation of multiwall carbon nanotubes (MWCNTs) which improve the characteristics of the electrodes. The electrodes were constructed based on gentamicin-phosphotungstate (GNS-PTA) called CPE1, gentamicin-phosphomolybdate (GNS-PMA) called CPE2, GNS-PTA+ MWMCNTs called MWCPE1, and GNS-PMA+ MWMCNTs called MWCPE2. The constructed electrodes, at optimum paste composition, exhibited good Nernstian response for determination of gentamicin sulfate (GNS) over a linear concentration range from 2.5×10(-6) to 1×10(-2), 3.0×10(-6) to 1×10(-2), 4.9×10(-7) to 1×10(-2) and 5.0×10(-7) to 1×10(-2)molL(-1), with lower detection limit 1×10(-6), 1×10(-6), 1.9×10(-7) and 2.2×10(-7)molL(-1), and with slope values of 29.0±0.4, 29.2±0.7, 31.2±0.5 and 31.0±0.6mV/decade for CPE1, CPE2, MWCPE1 and MWCPE2, respectively. The response of electrodes is not affected by pH in the range 3-8 for CPE1 and CPE2 and in the range 2.5-8.5 for MWCPE1 and MWCPE2. The results showed fast dynamic response time (about 8-5s) and long lifetime (more than 2months) for all electrodes. The sensors showed high selectivity for gentamicin sulfate (GNS) with respect to a large number of interfering species. The constructed electrodes were successfully applied for determination of GNS in pure form, its pharmaceutical preparations and biological fluids using standard addition and potentiometric titration methods with high accuracy and precision. Published by Elsevier B.V.

  9. Transtympanic gentamicin and fibrin tissue adhesive for treatment of unilateral Menière's disease: effects on vestibular function.

    PubMed

    Casani, Augusto; Nuti, Daniele; Franceschini, Stefano Sellari; Gaudini, Elisa; Dallan, Iacopo

    2005-12-01

    To determine the effects of transtympanic injections, with a mixture composed of gentamicin and fibrin tissue adhesive (FTA), on vestibular function of patients with intractable unilateral Menière's disease. This was an open, prospective study. The study was performed at 2 tertiary referral centers. Twenty-six patients affected by "definite" unilateral Menière's disease, unresponsive to medical therapy for at least 6 months, were enrolled. A buffered gentamicin solution mixed with FTA was injected in the middle ear until the development of bedside vestibular hypofunction signs and/or caloric weakness in the treated ear. Vestibular function was evaluated by 3 bedside vestibular tests (observation of spontaneous nystagmus, head shaking test, and head thrust test) and by a caloric test. Tests were performed on days 10 and 30 after completion of treatment. Tests were also performed 3, 6, and 12 months from completion of the gentamicin-FTA protocol. The effects of treatment were also assessed in terms of hearing levels, control of vertigo, and disability status. In 22 of the 26 patients, only 1 gentamicin-FTA injection was necessary to obtain 1 or more signs indicating a reduction of the vestibular function in the treated ear. Four patients needed another treatment because of the persistence of their incapacitating symptoms during the follow-up. Four patients needed more than 1 injection to obtain a vestibular hypofunction. None of the patients who received 1 or 2 injections presented hearing loss in direct temporal relationship to the treatment. A mixture of gentamicin and fibrin glue makes it possible to considerably reduce the number of administrations in patients with intractable unilateral Menière's disease. Spontaneous nystagmus, post head shaking nystagmus, and a head thrust sign are the clinical signs that indicate onset or progression of unilateral vestibular hypofunction. These signs were obtained with only 1 injection in 81% of patients.

  10. Aminoglycoside inhibition of Staphylococcus aureus biofilm formation is nutrient dependent

    PubMed Central

    Hess, Donavon J.; Wells, Carol L.

    2014-01-01

    Biofilms represent microbial communities, encased in a self-produced matrix or extracellular polymeric substance. Microbial biofilms are likely responsible for a large proportion of clinically significant infections and the multicellular nature of biofilm existence has been repeatedly associated with antibiotic resistance. Classical in vitro antibiotic-susceptibility testing utilizes artificial growth media and planktonic microbes, but this method may not account for the variability inherent in environments subject to biofilm growth in vivo. Experiments were designed to test the hypothesis that nutrient concentration can modulate the antibiotic susceptibility of Staphylococcus aureus biofilms. Developing S. aureus biofilms initiated on surgical sutures, and in selected experiments planktonic cultures, were incubated for 16 h in 66 % tryptic soy broth, 0.2 % glucose (1× TSBg), supplemented with bactericidal concentrations of gentamicin, streptomycin, ampicillin or vancomycin. In parallel experiments, antibiotics were added to growth medium diluted one-third (1/3× TSBg) or concentrated threefold (3× TSBg). Following incubation, viable bacteria were enumerated from planktonic cultures or suture sonicates, and biofilm biomass was assayed using spectrophotometry. Interestingly, bactericidal concentrations of gentamicin (5 µg gentamicin ml−1) and streptomycin (32 µg streptomycin ml−1) inhibited biofilm formation in samples incubated in 1/3× or 1× TSBg, but not in samples incubated in 3× TSBg. The nutrient dependence of aminoglycoside susceptibility is not only associated with biofilm formation, as planktonic cultures incubated in 3× TSBg in the presence of gentamicin also showed antibiotic resistance. These findings appeared specific for aminoglycosides because biofilm formation was inhibited in all three growth media supplemented with bactericidal concentrations of the cell wall-active antibiotics, ampicillin and vancomycin. Additional experiments showed that the ability of 3× TSBg to overcome the antibacterial effects of gentamicin was associated with decreased uptake of gentamicin by S. aureus. Uptake is known to be decreased at low pH, and the kinetic change in pH of growth medium from biofilms incubated in 5 µg gentamicin ml−1 in the presence of 3× TSBg was decreased when compared with pH determinations from biofilms formed in 1/3× or 1× TSBg. These studies underscore the importance of environmental factors, including nutrient concentration and pH, on the antibiotic susceptibility of S. aureus planktonic and biofilm bacteria. PMID:24696518

  11. Tailoring the Optical Properties of Silicon with Ion Beam Created Nanostructures for Advanced Photonics Applications

    NASA Astrophysics Data System (ADS)

    Akhter, Perveen

    In today's fast life, energy consumption has increased more than ever and with that the demand for a renewable and cleaner energy source as a substitute for the fossil fuels has also increased. Solar radiations are the ultimate source of energy but harvesting this energy in a cost effective way is a challenging task. Si is the dominating material for microelectronics and photovoltaics. But owing to its indirect band gap, Si is an inefficient light absorber, thus requiring a thickness of solar cells beyond tens of microns which increases the cost of solar energy. Therefore, techniques to increase light absorption in thin film Si solar cells are of great importance and have been the focus of research for a few decades now. Another big issue of technology in this fast-paced world is the computing rate or data transfer rate between components of a chip in ultra-fast processors. Existing electronic interconnects suffering from the signal delays and heat generation issues are unable to handle high data rates. A possible solution to this problem is in replacing the electronic interconnects with optical interconnects which have large data carrying capacity. However, optical components are limited in size by the fundamental laws of diffraction to about half a wavelength of light and cannot be combined with nanoscale electronic components. Tremendous research efforts have been directed in search of an advanced technology which can bridge the size gap between electronic and photonic worlds. An emerging technology of "plasmonics'' which exploits the extraordinary optical properties of metal nanostructures to tailor the light at nanoscale has been considered a potential solution to both of the above-mentioned problems. Research conducted for this dissertation has an overall goal to investigate the optical properties of silicon with metal nanostructures for photovoltaics and advanced silicon photonics applications. The first part of the research focuses on achieving enhanced light trapping in poly-Si thin films using ion implantation induced surface texturing. In addition to surface texturing produced by H and Ar ion implantations, metal nanostructures are also added to the surface to further suppress light reflection at the plasmonic resonance of metal nanostructures. Remarkable suppression has been achieved resulting in reflection from the air/Si interface to below ˜5%. In the second part, optical properties of embedded metal nanostructures in silicon matrix gettered into the ion implantation created nanocavities are studied. Embedded nanostructures can have a huge impact in future photonics applications by replacing the existing electronic and photonic components such as interconnects, waveguides, modulators and amplifiers with their plasmonic counterparts. This new method of encapsulating metal nanostructures in silicon is cost-effective and compatible with silicon fabrication technology. Spectroscopic ellipsometry is used to study the dielectric properties of silicon with embedded silver nanostructures. High absorption regions around 900 nm, corresponding to plasmonic absorption of Ag nanoparticles in Si, have been observed and compared to theoretical calculations and simulation results. The possibility of modifying the dielectric function of Si with metal nanostructures can lay the foundation for functional base structures for advanced applications in silicon photonics, photovoltaics and plasmonics.

  12. Nanochemistry of Protein-Based Delivery Agents

    PubMed Central

    Rajendran, Subin R. C. K.; Udenigwe, Chibuike C.; Yada, Rickey Y.

    2016-01-01

    The past decade has seen an increased interest in the conversion of food proteins into functional biomaterials, including their use for loading and delivery of physiologically active compounds such as nutraceuticals and pharmaceuticals. Proteins possess a competitive advantage over other platforms for the development of nanodelivery systems since they are biocompatible, amphipathic, and widely available. Proteins also have unique molecular structures and diverse functional groups that can be selectively modified to alter encapsulation and release properties. A number of physical and chemical methods have been used for preparing protein nanoformulations, each based on different underlying protein chemistry. This review focuses on the chemistry of the reorganization and/or modification of proteins into functional nanostructures for delivery, from the perspective of their preparation, functionality, stability and physiological behavior. PMID:27489854

  13. Carbonaceous nanowire supports for polymer electrolyte membrane fuel cells

    DOE PAGES

    Garzon, Fernando H.; Wilson, Mahlon S.; Banham, Dustin; ...

    2015-12-03

    Here, carbohydrate-dye combinations were used to form ionically-linked soft templates for the formation of polypyrrole nanowire networks. High yields of nanostructured products were obtained using small amounts of low-cost carbohydrate and dye template materials, the majority of which remained encapsulated within the nanowires. Varying the concentration and the two-part ratio of the templates influenced the length and diameter of the nanofiber segments within the nanowire network. Pyrolysis of the nanowires yielded carbonaceous fibers containing nitrogen heteroatoms, as well as convoluted graphitic domains, well suited for supporting Pt nanoparticles. The resulting high density of nucleation sites enabled the formation of wellmore » dispersed, smaller Pt particles compared to commercial catalysts, despite significantly higher support surface loadings.« less

  14. Nanochemistry of protein-based delivery agents

    NASA Astrophysics Data System (ADS)

    Rajendran, Subin; Udenigwe, Chibuike; Yada, Rickey

    2016-07-01

    The past decade has seen an increased interest in the conversion of food proteins into functional biomaterials, including their use for loading and delivery of physiologically active compounds such as nutraceuticals and pharmaceuticals. Proteins possess a competitive advantage over other platforms for the development of nanodelivery systems since they are biocompatible, amphipathic, and widely available. Proteins also have unique molecular structures and diverse functional groups that can be selectively modified to alter encapsulation and release properties. A number of physical and chemical methods have been used for preparing protein nanoformulations, each based on different underlying protein chemistry. This review focuses on the chemistry of the reorganization and/or modification of proteins into functional nanostructures for delivery, from the perspective of their preparation, functionality, stability and physiological behavior.

  15. Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.

    PubMed

    Mir, Fatima; Nisar, Imran; Tikmani, Shiyam S; Baloch, Benazir; Shakoor, Sadia; Jehan, Fyezah; Ahmed, Imran; Cousens, Simon; Zaidi, Anita K M

    2017-02-01

    Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection. We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0-59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429. Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and 817 (753 per protocol) were assigned procaine benzylpenicillin, gentamicin, and amoxicillin. Treatment failure within 7 days of enrolment was reported in 90 (12%) infants who received procaine benzylpenicillin and gentamicin (reference), 76 (10%) of those given amoxicillin and gentamicin (risk difference with reference -1·9, 95% CI -5·1 to 1·3), and 99 (13%) of those treated with procaine benzylpenicillin, gentamicin, and amoxicillin (risk difference with reference 1·1, -2·3 to 4·5). Two simplified antibiotic regimens requiring fewer injections are equivalent to a reference treatment for young infants with signs of clinical severe infection but without signs of critical illness. The use of these simplified regimens has the potential to increase access to treatment for sick young infants who cannot be referred to hospital. The Saving Newborn Lives initiative of Save the Children, through support from the Bill & Melinda Gates, and by WHO and USAID. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

  16. 21 CFR 524.1044a - Gentamicin ophthalmic solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin ophthalmic solution. 524.1044a Section 524.1044a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs and cats for the...

  17. 21 CFR 524.1044a - Gentamicin ophthalmic solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin ophthalmic solution. 524.1044a Section 524.1044a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs and cats for the...

  18. Binding of Aminoglycoside Antibiotics to Filtration Materials

    PubMed Central

    Wagman, Gerald H.; Bailey, Janet V.; Weinstein, Marvin J.

    1975-01-01

    An investigation to study adsorption of gentamicin and other related aminoglycoside antibiotics to cellulose, diatomaceous earth (Celite), and Seitz filter sheets was carried out. Experiments with five aminoglycosides indicated that 30 to 100% of these antibiotics was adsorbed to cellulose depending on the ratio of antibiotic to adsorbent, and the total quantity could not be removed by acidification. Similarly, a study with gentamicin found adsorption to diatomaceous earth to be in the range of 33 to 98%. Neomycin and gentamicin were also readily adsorbed to Seitz filter sheets. The data indicate that large losses may occur during filtration of these antibiotics under certain conditions, and care should be taken to properly evaluate results during studies with these compounds in the presence of adsorbent materials. PMID:1137384

  19. Binding of aminoglycoside antibiotics to filtration materials.

    PubMed

    Wagman, G H; Bailey, J V; Weinstein, M J

    1975-03-01

    An investigation to study adsorption of gentamicin and other related aminoglycoside antibiotics to cellulose, diatomaceous earth (Celite), and Seitz filter sheets was carried out. Experiments with five aminoglycosides indicated that 30 to 100% of these antibiotics was adsorbed to cellulose depending on the ratio of antibiotic to adsorbent, and the total quantity could not be removed by acidification. Similarly, a study with gentamicin found adsorption to diatomaceous earth to be in the range of 33 to 98%. Neomycin and gentamicin were also readily adsorbed to Seitz filter sheets. The data indicate that large losses may occur during filtration of these antibiotics under certain conditions, and care should be taken to properly evaluate results during studies with these compounds in the presence of adsorbent materials.

  20. Full and Broad-Spectrum In Vivo Eradication of Catheter-Associated Biofilms Using Gentamicin-EDTA Antibiotic Lock Therapy

    PubMed Central

    Chauhan, Ashwini; Lebeaux, David; Ghigo, Jean-Marc

    2012-01-01

    Biofilms that develop on indwelling devices are a major concern in clinical settings. While removal of colonized devices remains the most frequent strategy for avoiding device-related complications, antibiotic lock therapy constitutes an adjunct therapy for catheter-related infection. However, currently used antibiotic lock solutions are not fully effective against biofilms, thus warranting a search for new antibiotic locks. Metal-binding chelators have emerged as potential adjuvants due to their dual anticoagulant/antibiofilm activities, but studies investigating their efficiency were mainly in vitro or else focused on their effects in prevention of infection. To assess the ability of such chelators to eradicate mature biofilms, we used an in vivo model of a totally implantable venous access port inserted in rats and colonized by either Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, or Pseudomonas aeruginosa. We demonstrate that use of tetrasodium EDTA (30 mg/ml) as a supplement to the gentamicin (5 mg/ml) antibiotic lock solution associated with systemic antibiotics completely eradicated Gram-positive and Gram-negative bacterial biofilms developed in totally implantable venous access ports. Gentamicin-EDTA lock was able to eliminate biofilms with a single instillation, thus reducing length of treatment. Moreover, we show that this combination was effective for immunosuppressed rats. Lastly, we demonstrate that a gentamicin-EDTA lock is able to eradicate the biofilm formed by a gentamicin-resistant strain of methicillin-resistant S. aureus. This in vivo study demonstrates the potential of EDTA as an efficient antibiotic adjuvant to eradicate catheter-associated biofilms of major bacterial pathogens and thus provides a promising new lock solution. PMID:23027191

  1. The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.

    PubMed

    Gilmer, Daniel B; Schmitz, Jonathan E; Thandar, Mya; Euler, Chad W; Fischetti, Vincent A

    2017-01-01

    Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by <3-logs. A combination of 0.05 mg PlySs2 + 0.05 mg gentamicin reduced S. suis by >5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans.

  2. The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa

    PubMed Central

    Gilmer, Daniel B.; Schmitz, Jonathan E.; Thandar, Mya; Euler, Chad W.; Fischetti, Vincent A.

    2017-01-01

    Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by <3-logs. A combination of 0.05 mg PlySs2 + 0.05 mg gentamicin reduced S. suis by >5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans. PMID:28046082

  3. Antimicrobial effects of lysophosphatidylcholine on methicillin-resistant Staphylococcus aureus.

    PubMed

    Miyazaki, Haruko; Midorikawa, Naoko; Fujimoto, Saki; Miyoshi, Natsumi; Yoshida, Hideto; Matsumoto, Tetsuya

    2017-07-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is an important health care-associated and community-associated pathogen and causes a large number of infections worldwide. For the purpose of application to topical treatment of MRSA infection, we examined the antimicrobial effects of lysophosphatidylcholine (LPC) on MRSA strains. We also investigated the combination effect of LPC and gentamicin on MRSA growth. The LPC minimum inhibitory concentrations (MIC) for Gram-positive ( S. aureus, Staphylococcus epidermidis , and Streptococcus pneumoniae ) and Gram-negative ( Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae , and Pseudomonas aeruginosa ) bacteria were measured by the broth microdilution method. The mechanism of LPC-mediated MRSA killing was investigated by membrane permeability analysis with DiSC3(5) fluorescence and growth curve analysis. Lastly, the effects of LPC on gentamicin-induced bactericidal activity were determined in combination treatment studies with 15 gentamicin-resistant MRSA isolates from the skin, nose, or ears. The LPC MIC for Gram-positive bacteria varied between 32 µg/ml and >2048 µg/ml, whereas that for all Gram-negative bacteria was >2048 µg/ml. Consistently, membrane permeability analysis showed that LPC was substantially more effective in inducing membrane permeability in Gram-positive bacteria than in Gram-negative counterparts. Growth curve analysis in cotreatment studies demonstrated that LPC has intrinsic bactericidal effects and can also potentiate gentamicin sensitivity in resistant MRSA strains. Our study demonstrates that LPC exhibits intrinsic antimicrobial effects and can enhance the antimicrobial effects of gentamicin for resistant MRSA strains, suggesting that LPC may be a beneficial additive in topical antibiotics for superficial skin infections.

  4. Antimicrobial effects of lysophosphatidylcholine on methicillin-resistant Staphylococcus aureus

    PubMed Central

    Miyazaki, Haruko; Midorikawa, Naoko; Fujimoto, Saki; Miyoshi, Natsumi; Yoshida, Hideto; Matsumoto, Tetsuya

    2017-01-01

    Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is an important health care-associated and community-associated pathogen and causes a large number of infections worldwide. For the purpose of application to topical treatment of MRSA infection, we examined the antimicrobial effects of lysophosphatidylcholine (LPC) on MRSA strains. We also investigated the combination effect of LPC and gentamicin on MRSA growth. Methods: The LPC minimum inhibitory concentrations (MIC) for Gram-positive (S. aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae) and Gram-negative (Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa) bacteria were measured by the broth microdilution method. The mechanism of LPC-mediated MRSA killing was investigated by membrane permeability analysis with DiSC3(5) fluorescence and growth curve analysis. Lastly, the effects of LPC on gentamicin-induced bactericidal activity were determined in combination treatment studies with 15 gentamicin-resistant MRSA isolates from the skin, nose, or ears. Results: The LPC MIC for Gram-positive bacteria varied between 32 µg/ml and >2048 µg/ml, whereas that for all Gram-negative bacteria was >2048 µg/ml. Consistently, membrane permeability analysis showed that LPC was substantially more effective in inducing membrane permeability in Gram-positive bacteria than in Gram-negative counterparts. Growth curve analysis in cotreatment studies demonstrated that LPC has intrinsic bactericidal effects and can also potentiate gentamicin sensitivity in resistant MRSA strains. Conclusions: Our study demonstrates that LPC exhibits intrinsic antimicrobial effects and can enhance the antimicrobial effects of gentamicin for resistant MRSA strains, suggesting that LPC may be a beneficial additive in topical antibiotics for superficial skin infections. PMID:28748087

  5. Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats.

    PubMed

    Lakhera, Abhijeet; Ganeshpurkar, Aditya; Bansal, Divya; Dubey, Nazneen

    2015-06-01

    Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies. Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased creatinine levels in the animals, along with a decrease in serum urea and blood urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components.

  6. Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats

    PubMed Central

    Lakhera, Abhijeet; Bansal, Divya; Dubey, Nazneen

    2015-01-01

    Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies. Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased creatinine levels in the animals, along with a decrease in serum urea and blood urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components. PMID:27486367

  7. Middle ear gentamicin-soaked pledgets in the treatment of Ménière's disease.

    PubMed

    MacKeith, Samuel A C; Whiteside, Olivia J H; Mawby, Thomas; Bottrill, Ian D

    2014-02-01

    Assess the relative efficacy and results of the round window hyaluronic acid pledget depot method for intratympanic gentamicin delivery in Ménière's disease. Retrospective case review. Tertiary referral hospital. Prospective symptomatic and audiologic data were collected on 28 patients undergoing intratympanic gentamicin therapy for Ménière's disease refractory to medical treatment between 2003 and 2009. All patients had the round window membrane exposed via a tympanomeatal flap, and any adhesions were removed. Hyaluronic acid pledgets soaked in 40 mg/ml of gentamicin were then packed into the round window niche and posterior mesotympanum, and the tympanomeatal flap was replaced. Patients audiologic and vertigo symptom outcome scores were recorded at follow-up according to the AAO-HNS 1995 guidelines for reporting results in Ménière's disease. Complete or substantial improvement in vertigo (class A or B) was achieved in 88.5% (23/26) of patients. Hearing loss, defined as greater than 10 dB (PTA average at 0.5, 1, 2, and 4 kHz) was noted in 12 (50%) of 24 patients including 4 patients who had developed "dead ears" (16%). The average hearing loss for all patients excluding the 4 patients with dead ears was 10.7 dB. Round window hyaluronic acid pledget technique used as a sustained delivery vehicle for intratympanic gentamicin treatment for Ménière's disease produces similar rates of vertigo control compared with other techniques but a greater risk of hearing loss. We would recommend the intratympanicinjection titration technique as first line for most patients.

  8. Differential Expression of Unconventional Myosins in Apoptotic and Regenerating Chick Hair Cells Confirms Two Regeneration Mechanisms

    PubMed Central

    DUNCAN, LUKE J.; MANGIARDI, DOMINIC A.; MATSUI, JONATHAN I.; ANDERSON, JULIA K.; McLAUGHLIN-WILLIAMSON, KATE; COTANCHE, DOUGLAS A.

    2008-01-01

    Hair cells of the inner ear are damaged by intense noise, aging, and aminoglycoside antibiotics. Gentamicin causes oxidative damage to hair cells, inducing apoptosis. In mammals, hair cell loss results in a permanent deficit in hearing and balance. In contrast, avians can regenerate lost hair cells to restore auditory and vestibular function. This study examined the changes of myosin VI and myosin VIIa, two unconventional myosins that are critical for normal hair cell formation and function, during hair cell death and regeneration. During the late stages of apoptosis, damaged hair cells are ejected from the sensory epithelium. There was a 4–5-fold increase in the labeling intensity of both myosins and a redistribution of myosin VI into the stereocilia bundle, concurrent with ejection. Two separate mechanisms were observed during hair cell regeneration. Proliferating supporting cells began DNA synthesis 60 hours after gentamicin treatment and peaked at 72 hours postgentamicin treatment. Some of these mitotically produced cells began to differentiate into hair cells at 108 hours after gentamicin (36 hours after bromodeoxyuridine (BrdU) administration), as demonstrated by the colabeling of myosin VI and BrdU. Myosin VIIa was not expressed in the new hair cells until 120 hours after gentamicin. Moreover, a population of supporting cells expressed myosin VI at 78 hours after gentamicin treatment and myosin VIIa at 90 hours. These cells did not label for BrdU and differentiated far too early to be of mitotic origin, suggesting they arose by direct transdifferentiation of supporting cells into hair cells. PMID:17048225

  9. Refractory episodic vertigo: role of intratympanic gentamicin and vestibular evoked myogenic potentials.

    PubMed

    Celis-Aguilar, Erika; Hinojosa-González, Ramon; Vales-Hidalgo, Olivia; Coutinho-Toledo, Heloisa

    Even today, the treatment of intractable vertigo remains a challenge. Vestibular ablation with intratympanic gentamicin stands as a good alternative in the management of refractory vertigo patients. To control intractable vertigo through complete saccular and horizontal canal vestibular ablation with intratympanic gentamicin treatment. Patients with refractory episodic vertigo were included. The inclusion criteria were: unilateral ear disease, moderate to profound sensorineural hearing loss, and failure to other treatments. Included patients underwent 0.5-0.8mL of gentamicin intratympanic application at a 30mg/mL concentration. Vestibular ablation was confirmed by the absence of response on cervical vestibular evoked myogenic potentials and no response on caloric tests. Audiometry, electronystagmography with iced water, and vestibular evoked myogenic potentials were performed in all patients. Ten patients were included; nine patients with Meniere's disease and one patient with (late onset) delayed hydrops. Nine patients showed an absent response on vestibular evoked myogenic potentials and no response on caloric tests. The only patient with low amplitude on cervical vestibular evoked myogenic potentials had vertigo recurrence. Vertigo control was achieved in 90% of the patients. One patient developed hearing loss >30dB. Cervical vestibular evoked myogenic potentials confirmed vestibular ablation in patients treated with intratympanic gentamicin. High-grade vertigo control was due to complete saccular and horizontal canal ablation (no response to iced water in electronystagmography and no response on cervical vestibular evoked myogenic potentials). Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  10. 21 CFR 522.1044 - Gentamicin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 100 mg/mL solution in chickens and turkeys as in paragraphs (d)(2) and (d)(3) of this section. (2) No... mg/mL solution in turkeys as in paragraph (d)(2) and in chickens as in paragraph (d)(3) of this... food for at least 9 weeks after treatment. (3) Chickens—(i) Amount. 0.2 milligram of gentamicin per 0.2...

  11. 21 CFR 522.1044 - Gentamicin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 100 mg/mL solution in chickens and turkeys as in paragraphs (d)(2) and (d)(3) of this section. (2) No... mg/mL solution in turkeys as in paragraph (d)(2) and in chickens as in paragraph (d)(3) of this... food for at least 9 weeks after treatment. (3) Chickens—(i) Amount. 0.2 milligram of gentamicin per 0.2...

  12. 21 CFR 522.1044 - Gentamicin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 100 mg/mL solution in chickens and turkeys as in paragraphs (d)(2) and (d)(3) of this section. (2) No... mg/mL solution in turkeys as in paragraph (d)(2) and in chickens as in paragraph (d)(3) of this... food for at least 9 weeks after treatment. (3) Chickens—(i) Amount. 0.2 milligram of gentamicin per 0.2...

  13. Damage and Recovery of Hair Cells in Fish Canal (But Not Superficial) Neuromasts after Gentamicin Exposure

    NASA Technical Reports Server (NTRS)

    Song, Jiakun; Yan, Hong Young; Popper, Arthur N.

    1995-01-01

    Recent evidence demonstrating the presence of two types of sensory hair cells in the ear of a telcost fish (Astronotus ocellatus, the oscar) indicates that hair cell heterogeneity may exist not only in amniotic vertebrates but also in anamniotes. Here we report that a similar heterogeneity between hair cell types may also occur in the other mechanosensory organ of the oscar, the lateral line. We exposed oscars to the aminoglycoside (ototoxic) antibiotic gentamicin sulfate and found damaged sensory hair cells in one class of the lateral line receptors, the canal neuromasts, but not in the other class, the superficial neuromasts. This effect was not due to the canal environment. Moreover, new ciliary bundles on hair cells of the canal neuromasts were found after, and during, gentamicin exposure. The pattern of hair cell destruction and recovery in canal neuromasts is similar to that of type 1-like hair cells found in the striolar region of the utricle and lagena of the oscar after gentamicin treatment. These results suggest that the hair cells in the canal and superficial neuromasts may be similar to type 1-like and type 2 hair cells, respectively, in the fish ear.

  14. High-level penicillin resistance and penicillin-gentamicin synergy in Enterococcus faecium.

    PubMed Central

    Torres, C; Tenorio, C; Lantero, M; Gastañares, M J; Baquero, F

    1993-01-01

    Thirty-seven Enterococcus faecium strains with different levels of penicillin susceptibility were studied in time-kill experiments with a fixed concentration (5 micrograms/ml) of gentamicin combined with different penicillin concentrations (6 to 600 micrograms/ml). Synergy was defined as a relative decrease in counts of greater than 2 log10 CFU per milliliter after 24 h of incubation when the combination of the antibiotics was compared with its most active component alone. The minimal synergistic penicillin concentrations found were 6 micrograms/ml for 16 of 16 strains for which penicillin MICs were < or = 25 micrograms/ml, 20 to 100 micrograms/ml for 14 of 17 strains for which penicillin MICs were 50 to 200 micrograms/ml, and 200 to 500 micrograms/ml for 4 of 4 strains for which MICs penicillin were > 200 micrograms/ml. Penicillin-gentamicin synergy was observed even in high-level penicillin-resistant E. faecium strains at penicillin concentrations close to one-half the penicillin MIC. The possibility of treating infections caused by high-level penicillin-resistant E. faecium strains with penicillin-gentamicin combinations in particular cases may depend on the penicillin levels attainable in vivo. PMID:8285628

  15. Use of a gentamicin-impregnated collagen sheet (Collatamp(®)) in the management of major soft tissue complications in pediatric cochlear implants.

    PubMed

    Benito-González, Fernando; Benito, Jose; Sánchez, Luis Alberto Guardado; Estevez Alonso, Santiago; Muñoz Herrera, Angel; Batuecas-Caletrio, Angel

    2014-09-01

    The objective was to report the effectiveness of salvage treatment in soft tissue infection around cochlear implants with an absorbable gentamicin collagen sheet and a periosteum and skin rotation flaps. Three patients with cochlear implant and persistent surrounding soft tissue infection are included. All of them underwent antibiotic treatment prior to surgery without any response. In this study preoperative and postoperative audiograms were practiced. Surgical excision of infectious skin and a periosteum and skin rotation flaps were performed. The cochlear implant was refixed in the temporal bone and a gentamicin-impregnated collagen sheet was located covering the cochlear implant. headings In all patients with soft tissue infection around the cochlear implant, infection was completely resolved. It was not necessary to remove the device in any case. The use of an absorbable gentamicin-impregnated collagen sheet is not described for the management of soft tissue complications in pediatric cochlear implant patients. The local application of high concentrations of antibiotic administered by this sheet may be effective against resistant bacteria and, in conjunction with surgery, may resolve this type of complications.

  16. Optimizing photodynamic therapy by liposomal formulation of the photosensitizer pyropheophorbide-a methyl ester: in vitro and ex vivo comparative biophysical investigations in a colon carcinoma cell line.

    PubMed

    Guelluy, Pierre-Henri; Fontaine-Aupart, Marie-Pierre; Grammenos, Angeliki; Lécart, Sandrine; Piette, Jacques; Hoebeke, Maryse

    2010-09-24

    Photodynamic therapy (PDT), induced by a photosensitizer (PS) encapsulated in a nanostructure, has emerged as an appropriate treatment to cure a multitude of oncological and non-oncological diseases. Pyropheophorbide-a methyl ester (PPME) is a second-generation PS tested in PDT, and is a potential candidate for future clinical applications. The present study, carried out in a human colon carcinoma cell line (HCT-116), evaluates the improvement resulting from a liposomal formulation of PPME versus free-PPME. Absorption and fluorescence spectroscopies, fluorescence lifetime measurements, subcellular imaging and co-localization analysis have been performed in order to analyze the properties of PPME for each delivery mode. The benefit of drug encapsulation in DMPC-liposomes is clear from our experiments, with a 5-fold higher intracellular drug delivery than that observed with free-PPME at similar concentrations. The reactive oxygen species (ROSs) produced after PPME-mediated photosensitization have been identified and quantified by using electron spin resonance spectroscopy. Our results demonstrate that PPME-PDT-mediated ROSs are composed of singlet oxygen and a hydroxyl radical. The small amounts of PPME inside mitochondria, as revealed by fluorescence co-localization analysis, could maybe explain the very low apoptotic cell death measured in HCT-116 cells.

  17. Fluorescence-tagged amphiphilic brush copolymer encapsulated Gd2O3 core-shell nanostructures for enhanced T 1 contrast effect and fluorescent imaging

    NASA Astrophysics Data System (ADS)

    Wang, Fenghe; Peng, Erwin; Liu, Feng; Li, Pingjing; Fong Yau Li, Sam; Xue, Jun Min

    2016-10-01

    To obtain suitable T 1 contrast agents for magnetic resonance imaging (MRI) application, aqueous Gd2O3 nanoparticles (NPs) with high longitudinal relativity (r 1) are demanded. High quality Gd2O3 NPs are usually synthesized through a non-hydrolytic route which requires post-synthetic modification to render the NPs water soluble. The current challenge is to obtain aqueous Gd2O3 NPs with high colloidal stability and enhanced r 1 relaxivity. To overcome this challenge, fluorescence-tagged amphiphilic brush copolymer (AFCP) encapsulated Gd2O3 NPs were proposed as suitable T 1 contrast agents. Such a coating layer provided (i) superior aqueous stability, (ii) biocompatibility, as well as (iii) multi-modality (conjugation with fluorescence dye). The polymeric coating layer thickness was simply adjusted by varying the phase-transfer parameters. By reducing the coating thickness, i.e. the distance between the paramagnetic centre and surrounding water protons, the r 1 relaxivity could be enhanced. In contrast, a thicker polymeric layer coating prevents Gd3+ ions leakage, thus improving its biocompatibility. Therefore, it is important to strike a balance between the biocompatibility and the r 1 relaxivity behaviour. Lastly, by conjugating fluorescence moiety, an additional imaging modality was enabled, as demonstrated from the cell-labelling experiment.

  18. Using DNA nanotechnology to produce a drug delivery system

    NASA Astrophysics Data System (ADS)

    Huyen La, Thi; Thu Thuy Nguyen, Thi; Phuc Pham, Van; Huyen Nguyen, Thi Minh; Huan Le, Quang

    2013-03-01

    Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October-2 November, 2012, Ha Long, Vietnam.

  19. Fabrication of Silica-Coated Hollow Carbon Nanospheres Encapsulating Fe3O4 Cluster for Magnetical and MR Imaging Guided NIR Light Triggering Hyperthermia and Ultrasound Imaging.

    PubMed

    Huang, Yun-Kai; Su, Chia-Hao; Chen, Jiu-Jeng; Chang, Chun-Ting; Tsai, Yu-Hsin; Syu, Sheng-Fu; Tseng, Tsu-Ting; Yeh, Chen-Sheng

    2016-06-15

    Iron oxide nanoparticles (IONPs)-carbon (C) hybrid zero-dimensional nanostructures normally can be categorized into core-shell and yolk-shell architectures. Although IONP-C is a promising theranostic nanoagent, the in vivo study has surprisingly been less described. In addition, little effort has strived toward the fabrication of yolk-shell compared to the core-shell structures. In this context, we synthesized a yolk-shell type of the silica-coated hollow carbon nanospheres encapsulating IONPs cluster, which can be dispersed in aqueous solution for systemic studies in vivo, via the preparation involving the mixed micellization, polymerization/hollowing, sol-gel (hydration-condensation), and pyrolysis processes. Through a surface modification of the polyethylenimine followed by the sol-gel process, the silica shell coating was able to escape from condensing and sintering courses resulting in aggregation, due to the annealing. Not limited to the well-known functionalities in magnetical targeting and magnetic resonance (MR) imaging for IONP-C hybrid structures, we expanded this yolk-shell NPs as a near-infrared (NIR) light-responsive echogenic nanoagent giving an enhanced ultrasound imaging. Overall, we fabricated the NIR sensitive yolk-shell IONP-C to activate ultrasound imaging and photothermal ablation under magnetically and MR imaging guided therapy.

  20. Shrink Wrapping Cells in a Defined Extracellular Matrix to Modulate the Chemo-Mechanical Microenvironment.

    PubMed

    Palchesko, Rachelle N; Szymanski, John M; Sahu, Amrita; Feinberg, Adam W

    2014-09-01

    Cell-matrix interactions are important for the physical integration of cells into tissues and the function of insoluble, mechanosensitive signaling networks. Studying these interactions in vitro can be difficult because the extracellular matrix (ECM) proteins that adsorb to in vitro cell culture surfaces do not fully recapitulate the ECM-dense basement membranes to which cells such as cardiomyocytes and endothelial cells adhere to in vivo . Towards addressing this limitation, we have developed a surface-initiated assembly process to engineer ECM proteins into nanostructured, microscale sheets that can be shrink wrapped around single cells and small cell ensembles to provide a functional and instructive matrix niche. Unlike current cell encapsulation technology using alginate, fibrin or other hydrogels, our engineered ECM is similar in density and thickness to native basal lamina and can be tailored in structure and composition using the proteins fibronectin, laminin, fibrinogen, and/or collagen type IV. A range of cells including C2C12 myoblasts, bovine corneal endothelial cells and cardiomyocytes survive the shrink wrapping process with high viability. Further, we demonstrate that, compared to non-encapsulated controls, the engineered ECM modulates cytoskeletal structure, stability of cell-matrix adhesions and cell behavior in 2D and 3D microenvironments.

  1. Shrink Wrapping Cells in a Defined Extracellular Matrix to Modulate the Chemo-Mechanical Microenvironment

    PubMed Central

    Palchesko, Rachelle N.; Szymanski, John M.; Sahu, Amrita; Feinberg, Adam W.

    2014-01-01

    Cell-matrix interactions are important for the physical integration of cells into tissues and the function of insoluble, mechanosensitive signaling networks. Studying these interactions in vitro can be difficult because the extracellular matrix (ECM) proteins that adsorb to in vitro cell culture surfaces do not fully recapitulate the ECM-dense basement membranes to which cells such as cardiomyocytes and endothelial cells adhere to in vivo. Towards addressing this limitation, we have developed a surface-initiated assembly process to engineer ECM proteins into nanostructured, microscale sheets that can be shrink wrapped around single cells and small cell ensembles to provide a functional and instructive matrix niche. Unlike current cell encapsulation technology using alginate, fibrin or other hydrogels, our engineered ECM is similar in density and thickness to native basal lamina and can be tailored in structure and composition using the proteins fibronectin, laminin, fibrinogen, and/or collagen type IV. A range of cells including C2C12 myoblasts, bovine corneal endothelial cells and cardiomyocytes survive the shrink wrapping process with high viability. Further, we demonstrate that, compared to non-encapsulated controls, the engineered ECM modulates cytoskeletal structure, stability of cell-matrix adhesions and cell behavior in 2D and 3D microenvironments. PMID:25530816

  2. Polyaniline-encapsulated silicon on three-dimensional carbon nanotubes foam with enhanced electrochemical performance for lithium-ion batteries

    NASA Astrophysics Data System (ADS)

    Zhou, Xiaoming; Liu, Yang; Du, Chunyu; Ren, Yang; Mu, Tiansheng; Zuo, Pengjian; Yin, Geping; Ma, Yulin; Cheng, Xinqun; Gao, Yunzhi

    2018-03-01

    Seeking free volume around nanostructures for silicon-based anodes has been a crucial strategy to improve cycling and rate performance in the next generation Li-ion batteries. Herein, through a simple pyrolysis and in-situ polymerization approach, the low cost commercially available melamine foam as a soft template converts carbon nanotubes into highly dispersed and three-dimensionally interconnected framework with encapsulated silicon/polyaniline hierarchical nanoarchitecture. This unique core-sheath structure based on carbon nanotubes foam integrates a large number of mesoporous, thus providing well-accessible space for electrolyte wetting, whereas the carbon nanotubes matrix serves as conductive thoroughfares for electron transport. Meanwhile, the outer polyaniline coated on silicon nanoparticles provides effective space for volume expansion of silicon, further inhibiting the active material escape from the current collector. As expected, the PANI-Si@CNTs foam exhibits a high initial specific capacity of 1954 mAh g-1 and retains 727 mAh g-1 after 100 cycles at 100 mA g-1, which can be attributed to highly electrical conductivity of carbon nanotubes and protective layer of polyaniline sheath, together with three-dimensionally interconnected porous skeleton. This facile structure can pave a way for large scale synthesis of high durable silicon-based anodes or other electrode materials with huge volume expansion.

  3. A Universal Strategy for Hollow Metal Oxide Nanoparticles Encapsulated into B/N Co-Doped Graphitic Nanotubes as High-Performance Lithium-Ion Battery Anodes.

    PubMed

    Tabassum, Hassina; Zou, Ruqiang; Mahmood, Asif; Liang, Zibin; Wang, Qingfei; Zhang, Hao; Gao, Song; Qu, Chong; Guo, Wenhan; Guo, Shaojun

    2018-02-01

    Yolk-shell nanostructures have received great attention for boosting the performance of lithium-ion batteries because of their obvious advantages in solving the problems associated with large volume change, low conductivity, and short diffusion path for Li + ion transport. A universal strategy for making hollow transition metal oxide (TMO) nanoparticles (NPs) encapsulated into B, N co-doped graphitic nanotubes (TMO@BNG (TMO = CoO, Ni 2 O 3 , Mn 3 O 4 ) through combining pyrolysis with an oxidation method is reported herein. The as-made TMO@BNG exhibits the TMO-dependent lithium-ion storage ability, in which CoO@BNG nanotubes exhibit highest lithium-ion storage capacity of 1554 mA h g -1 at the current density of 96 mA g -1 , good rate ability (410 mA h g -1 at 1.75 A g -1 ), and high stability (almost 96% storage capacity retention after 480 cycles). The present work highlights the importance of introducing hollow TMO NPs with thin wall into BNG with large surface area for boosting LIBs in the terms of storage capacity, rate capability, and cycling stability. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Pirbenicillin: Comparison with Carbenicillin and BL-P1654, Alone and with Gentamicin, Against Pseudomonas aeruginosa

    PubMed Central

    Lopez, Carlos E.; Standiford, Harold C.; Tatem, Beverly A.; Calia, Frank M.; Schimpff, Stephen C.; Snyder, Merrill J.; Hornick, Richard B.

    1977-01-01

    Minimum inhibitory concentrations (MIC) of pirbenicillin against 135 clinical isolates of Pseudomonas aeruginosa were one-fourth of those required for carbenicillin but two times higher than those for BL-P1654. Increasing the inoculum size produced an adverse effect on the bactericidal activity for all three antibiotics. This was more apparent for pirbenicillin than for carbenicillin, but less than the effect on BL-P1654. When concentrations of antibiotics likely to be achieved clinically were used, gentamicin increased the inhibitory and bactericidal effects of all three semisynthetic penicillins for the majority of isolates. Strains highly resistant to the aminoglycoside antibiotic, however, were inhibited no more by the penicillin-gentamicin combinations than by the most effective of the antibiotics alone. PMID:404963

  5. Interference of the antimicrobial peptide lactoferricin B with the action of various antibiotics against Escherichia coli and Staphylococcus aureus.

    PubMed

    Vorland, L H; Osbakk, S A; Perstølen, T; Ulvatne, H; Rekdal, O; Svendsen, J S; Gutteberg, T J

    1999-01-01

    The antimicrobial peptide, lactoferricin, can be generated upon gastric pepsin cleavage of lactoferrin. We have examined the interaction of lactoferricin of bovine origin, Lf-cin B, with the antibiotics penicillin G, vancomycin, gentamicin, colistin, D-cycloserine and erythromycin against E. coli ATCC 25922 and Staphylococcus aureus ATCC 25923. We demonstrated synergism between Lf-cin B and erythromycin against E. coli, and partial synergism between Lf-cin B and penicillin G, vancomycin and gentamicin against E. coli. Only penicillin G acted in partial synergism with Lf-cin B against S. aureus. Lf-cin B antagonized vancomycin and gentamicin against S. aureus in low concentration. We conclude that Lf-cin B may facilitate the uptake of antibiotics across the cell envelope.

  6. Amphiphilic Peptide Nanorods Based on Oligo-Phenylalanine as a Biocompatible Drug Carrier.

    PubMed

    Song, Su Jeong; Lee, Seulgi; Ryu, Kyoung-Seok; Choi, Joon Sig

    2017-09-20

    Peptide nanostructure has been widely explored for drug-delivery systems in recent studies. Peptides possess comparatively lower cytotoxicity and are more efficient than polymeric carriers. Here, we propose a peptide nanorod system, composed of an amphiphilic oligo-peptide RH 3 F 8 (Arg-His 3 -Phe 8 ), as a drug-delivery carrier. Arginine is an essential amino acid in typical cell-penetration peptides, and histidine induces endo- and lysosomal escape because of its proton sponge effect. Phenylalanine is introduced to provide rich hydrophobicity for stable self-assembly and drug encapsulation. The self-assembled structure of RH 3 F 8 showed nanorod-shaped morphology, positive surface charge, and retained formation in water for 35 days. RH 3 F 8 , labeled with Nile Red, showed high cellar uptake and accumulation in both cytoplasm and nucleus. The RH 3 F 8 nanorods demonstrated negligible cytotoxicity, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and hemolysis assays. To confirm the efficiency of drug delivery, curcumin was encapsulated in the RH 3 F 8 nanorod system (RH 3 F 8 -Cur). RH 3 F 8 -Cur showed high encapsulation efficiency (24.63%) under the conditions of 200 μM curcumin. The RH 3 F 8 -Cur retained nanoscale size and positive surface charge, similar to those of the empty RH 3 F 8 nanorods. RH 3 F 8 -Cur displayed a robust anticancer effect in HeLa and A549 cells, and inhibited the proliferation of cancer cells in a zebrafish model. These results indicate that the RH 3 F 8 nanorods may be a promising candidate for a safe and effective drug-delivery system.

  7. Laser-generated shockwaves enhance antibacterial activity against biofilms in vitro.

    PubMed

    Yao, William; Kuan, Edward C; Francis, Nathan C; St John, Maie A; Grundfest, Warren S; Taylor, Zachary D

    2017-07-01

    Bacterial biofilm formation within chronic wound beds, which provides an effective barrier against antibiotics, is a known cause of recalcitrant infections and a significant healthcare burden, often requiring repeated surgical debridements. Laser-generated shockwaves (LGS) is a novel, minimally invasive, and nonthermal modality for biofilm mechanical debridement which utilizes compressive stress waves, generated by photonic absorption in thin titanium films to mechanically disrupt the biofilm. Prior studies have demonstrated LGS monotherapy to be selectively efficacious for biofilm disruption and safe for host tissues. In this study, we sought to determine if LGS can enhance the antimicrobial activity and biofilm disruption capability of topical antibiotic therapy. Staphylococcus epidermidis biofilms grown in vitro on glass were treated with topical gentamicin (31, 62, and 124 μg/ml) with and without LGS (n = 3-11/treatment group). Mechanical shockwaves were generated with a 1,064 nm Nd:YAG laser (laser fluence 110.14 mJ/mm 2 , pulse duration 5 ns, spot size 3 mm). Following a 24-hour incubation period, bacterial viability was assessed by determining the number of colony-forming units (CFU) via the Miles and Misra method. Residual biofilm bioburden was analyzed using the crystal violet biofilm assay. With gentamicin monotherapy, CFU density (CFU/mm 2 ) at 31, 62, and 124 μg/ml were (282 ± 84) × 10 4 , (185 ± 34) × 10 4 , and (113 ± 9) × 10 4 , respectively. With LGS and gentamicin therapy, CFU density decreased to (170 ± 44) × 10 4 , (89 ± 24) × 10 4 , and (43 ± 3) × 10 4 , respectively (P = 0.1704, 0.0302, and 0.0004 when compared with gentamicin alone). Biofilm burden as measured by the assay in the gentamicin 31, 62, and 124 μg/ml groups was reduced by 80%, 95%, and 98% when LGS was added (P = 0.0102, >0.0001, and 0.0001 for all groups when compared with gentamicin alone). Furthermore, samples treated with LGS saw an increase in susceptibility to gentamicin, in terms of reduced biofilm bioburden and CFU densities. LGS enhances the efficacy of topical antibiotics in an in vitro model. This has significant implications for clinical applications in the management of chronic soft tissue infections and recalcitrant chronic rhinosinusitis. Lasers Surg. Med. 49:539-547, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Gentamicin versus ceftriaxone for the treatment of gonorrhoea (G-TOG trial): study protocol for a randomised trial.

    PubMed

    Brittain, Clare; Childs, Margaret; Duley, Lelia; Harding, Jan; Hepburn, Trish; Meakin, Garry; Montgomery, Alan A; Tan, Wei; Ross, Jonathan D C

    2016-11-24

    Gonorrhoea is a common sexually transmitted infection which causes genital pain and discomfort; in women it can also lead to pelvic inflammatory disease and infertility, and in men to epididymo-orchitis. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance which is reducing its effectiveness against gonorrhoea. A small, but increasing, number of patients have already been found to have highly resistant strains of gonorrhoea which has been associated with clinical failure. This trial aims to determine whether gentamicin is not clinically worse than ceftriaxone in the treatment of gonorrhoea. This is a blinded, two-arm, multicentre, noninferiority randomised trial. Patients are eligible if they are aged 16-70 years with a diagnosis of genital, pharyngeal and/or rectal gonorrhoea. Exclusion criteria are: known concurrent sexually transmitted infection(s) (excluding chlamydia); bacterial vaginosis and/or Trichomonas vaginalis infection; contraindications or an allergy to gentamicin, ceftriaxone, azithromycin or lidocaine; pregnancy or breastfeeding; complicated gonorrhoeal infection; weight under 40 kg; use of ceftriaxone, gentamicin or azithromycin within the preceding 28 days. Randomisation is to receive a single intramuscular injection of either gentamicin or ceftriaxone, all participants receive 1 g oral azithromycin as standard treatment. The estimated sample size is 720 participants (noninferiority limit 5%). The primary outcome is clearance of Neisseria gonorrhoeae at all infected sites by a negative Nucleic Acid Amplification Test, 2 weeks post treatment. Secondary outcomes include clinical resolution of symptoms, frequency of adverse events, tolerability of therapy, relationship between clinical effectiveness and antibiotic minimum inhibitory concentration for N. gonorrhoeae, and cost-effectiveness. The options for future treatment of gonorrhoea are limited. Results from this randomised trial will demonstrate whether gentamicin is not clinically worse than ceftriaxone for the treatment of gonorrhoea. This will inform clinical practice and policy for the treatment of gonorrhoea when current therapy with cephalosporins is no longer effective, or is contraindicated. International Standard Randomised Controlled Trial Number - ISRCTN51783227 , Registered on 18 September 2014. Current protocol version 2.0 17 June 2015.

  9. Gentamicin Nephrotoxicity in Subclinical Renal Disease.

    NASA Astrophysics Data System (ADS)

    Frazier, Donita L.

    The purpose of the present study was to examine the pharmacokinetic disposition of gentamicin and to define the mechanisms which predispose to nephrotoxicity in subclinical renal disease. Subtotally nephrectomized beagle dogs were used as a model for human beings with compromised renal function secondary to a reduced number of functional nephrons. Using ultrastructural morphometry, light microscopy and clinical chemistry data, the model was defined and the nephrotoxic responses of intact dogs administered recommended doses of drug were compared to the response of subtotally nephrectomized dogs administered reduced doses based on each animal's clearance of drug. Lysosomal and mitochondrial morphometric changes suggested mechanisms for increased sensitivity. To determine if increased sensitivity in this model was dependent on altered serum concentrations, variable rate infusions based on individual pharmacokinetic disposition of drug were administered using computer-driven infusion pumps. Identical serum concentration-time profiles were achieved in normal dogs and subtotally nephrectomized dogs, however, toxicity was significantly greater in nephrectomized dogs. The difference in the nephrotoxic response was characterized by administering supratherapeutic doses of drug to dogs. Nephrectomized dogs given a recommended dose of gentamicin became oliguric during the second week of treatment and increasingly uremic after withdrawal of drug. In contrast, intact dogs administered 2 times the recommended dose of gentamicin become only slightly polyuric during week 4 of treatment. The need to individualize dosage regimens based on drug clearance and not serum creatinine nor creatinine clearance alone was substantiated by describing the pharmacokinetic disposition of gentamicin in spontaneously occurring disease states. Four individualized dosage regimens with differing predicted efficacy were then administered to nephrectomized dogs to determine their relative nephrotoxic potential. Conclusions from these studies include (1) nephrectomized dogs are more susceptible to gentamicin-induced nephrotoxicity than intact dogs, (2) sensitivity is not totally dependent on serum drug concentrations, (3) nephrectomized dogs have hypertrophied nephrons with subcellular alterations in proximal tubule cells, (4) unlike intact dogs, the toxic response in nephrectomized dogs is characterized by oliguria and irreversibility, (5) dosage regimens of aminoglycosides should be based on individual drug disposition since it varies greatly in spontaneous disease states and (6) altered dosage regimens may decrease toxicity and increase efficacy.

  10. Improving intestinal absorption and oral bioavailability of curcumin via taurocholic acid-modified nanostructured lipid carriers.

    PubMed

    Tian, Cihui; Asghar, Sajid; Wu, Yifan; Chen, Zhipeng; Jin, Xin; Yin, Lining; Huang, Lin; Ping, Qineng; Xiao, Yanyu

    2017-01-01

    The expression of multiple receptors on intestinal epithelial cells enables an actively targeted carrier to significantly enhance the oral delivery of payloads. Conjugating the receptors' ligands on the surfaces of a particulate-delivery system allows site-specific targeting. Here, we used taurocholic acid (TCA) as a ligand for uptake of nanostructured lipid carriers (NLCs) mediated by a bile-acid transporter to improve oral bioavailability of curcumin (Cur). First, synthesis of TCA-polyethylene glycol 100-monostearate (S100-TCA) was carried out. Then, the physical and chemical properties of S100-TCA-modified Cur-loaded NLCs (Cur-TCA NLCs) with varying levels of S100-TCA modifications were investigated. Small particle size (<150 nm), high drug encapsulation (>90%), drug loading (about 3%), negative ζ-potential (-7 to -3 mV), and sustained release were obtained. In situ intestinal perfusion studies demonstrated improved absorption rate and permeability coefficient of Cur-TCA NLCs. Depending on the degree of modification, Cur-TCA NLCs displayed about a five- to 15-fold higher area under the curve in rats after oral administration than unmodified Cur NLCs, which established that the addition of S100-TCA to the NLCs boosted absorption of Cur. Further investigations of TCA NLCs might reveal a bright future for effective oral delivery of poorly bioavailable drugs.

  11. A Single-Step Hydrothermal Route to 3D Hierarchical Cu2 O/CuO/rGO Nanosheets as High-Performance Anode of Lithium-Ion Batteries.

    PubMed

    Wu, Songhao; Fu, Gaoliang; Lv, Weiqiang; Wei, Jiake; Chen, Wenjin; Yi, Huqiang; Gu, Meng; Bai, Xuedong; Zhu, Liang; Tan, Chao; Liang, Yachun; Zhu, Gaolong; He, Jiarui; Wang, Xinqiang; Zhang, Kelvin H L; Xiong, Jie; He, Weidong

    2018-02-01

    As anodes of Li-ion batteries, copper oxides (CuO) have a high theoretical specific capacity (674 mA h g -1 ) but own poor cyclic stability owing to the large volume expansion and low conductivity in charges/discharges. Incorporating reduced graphene oxide (rGO) into CuO anodes with conventional methods fails to build robust interaction between rGO and CuO to efficiently improve the overall anode performance. Here, Cu 2 O/CuO/reduced graphene oxides (Cu 2 O/CuO/rGO) with a 3D hierarchical nanostructure are synthesized with a facile, single-step hydrothermal method. The Cu 2 O/CuO/rGO anode exhibits remarkable cyclic and high-rate performances, and particularly the anode with 25 wt% rGO owns the best performance among all samples, delivering a record capacity of 550 mA h g -1 at 0.5 C after 100 cycles. The pronounced performances are attributed to the highly efficient charge transfer in CuO nanosheets encapsulated in rGO network and the mitigated volume expansion of the anode owing to its robust 3D hierarchical nanostructure. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Encapsulation of valproic acid and sodic phenytoin in ordered mesoporous SiO 2 solids for the treatment of temporal lobe epilepsy

    NASA Astrophysics Data System (ADS)

    López, T.; Basaldella, E. I.; Ojeda, M. L.; Manjarrez, J.; Alexander-Katz, R.

    2006-10-01

    Temporal lobe epilepsy is one of the most frequent types of human neurological diseases, and a variety of surgical procedures have been developed for the treatment of intractable cases. An alternative is the use of drug-containing reservoirs based on nanostructured materials of controlled pore sizes in order to deliver the drug without causing secondary effects. Ordered SiO 2 nanostructures were developed as drug reservoirs. The latter were prepared by the sol-gel process using tetraethyl orthosilicate TEOS as precursor to form the "sol" and P123 surfactant as the organic structure-directing agent. In addition to the nontoxic nature of amorphous silica, uniform and tunable pore sizes between 2.5 and 30 nm can be obtained in this way. The aim of this study is to investigate the potential of these materials for the storage and release of drugs in the brain. For that, we loaded valproic acid (VH) and sodic phenytoin (PH) molecules into an ordered mesoporous SiO 2 by impregnation and characterized the drug impregnated SiO 2 by standard physical and spectroscopic techniques to identify the parameters necessary to improve the capacity and quality of the reservoirs. Finally, a study of neurohistopathology of the effects of these reservoirs on brain tissue is presented.

  13. Synthesis of NiO-TiO2 hybrids/mSiO2 yolk-shell architectures embedded with ultrasmall gold nanoparticles for enhanced reactivity

    NASA Astrophysics Data System (ADS)

    Fang, Jiasheng; Zhang, Yiwei; Zhou, Yuming; Zhao, Shuo; Zhang, Chao; Huang, Mengqiu; Gao, Yan

    2017-08-01

    Novel NiO-TiO2 hybrids/mSiO2 yolk-shell architectures loaded with ultrasmall Au nanoparticles (STNVS-Au) were developed via the rational synthetic strategy. The hierarchical yolk-shell nanostructures (STNVS) with high surface areas were constructed by a facile "bottom-up" assembly process using SiO2 materials and polymer resins as cores/shells and sacrificial templates, accompanied by a simple hydrothermal incorporation of NiO into uniform amorphous TiO2 layers that were converted to NiO-anatase TiO2 p-n heterojunction hybrids. Then, numerous sub-3 nm Au nanoparticles were post encapsulated within STNVS nanostructures through the low-temperature hydrogen reduction based on the unique deposition-precipitation method with Au(en)2Cl3 compounds as gold precursors. The NiO-TiO2 hybrids alloying with Au nanoparticles were effectively protected and entrapped within STNVS architectures, and interacted with outer mSiO2-Au shells, which comprised the powerful STNVS-Au yolk-shell nanoreactors and produced stronger configural synergies in enhancing the heterogeneous catalysis. Into catalyzing the reduction of 4-nitrophenol to 4-aminophenol, the STNVS-Au was shown with outstanding activity and reusability, and its pristine morphology was well retained during the recycling process.

  14. Magnetic nanofibers with core (Fe 3O 4 nanoparticle suspension)/sheath (poly ethylene terephthalate) structure fabricated by coaxial electrospinning

    NASA Astrophysics Data System (ADS)

    Sung, Yun Kyung; Ahn, Byung Wook; Kang, Tae Jin

    2012-03-01

    One-dimensional magnetic nanostructures have recently attracted much attention because of their intriguing properties that are not realized by their bulk or particle form. These nanostructures are potentially useful for the application to ultrahigh-density data storages, sensors and bulletproof vest. The magnetic particles in magnetic nanofibers of blend types cannot fully align along the external magnetic field because magnetic particles are arrested in solid polymer matrix. To improve the mobility of magnetic particles, we used magneto-rheological fluid (MRF), which has the good mobility and dispersibility. Superparamagnetic core/sheath composite nanofibers were obtained with MRF and poly (ethylene terephthalate) (PET) solution via a coaxial electrospinning technique. Coaxial electrospinning is suited for fabricating core/sheath nanofibers encapsulating MRF materials within a polymer sheath. The magnetic nanoparticles in MRF were dispersed within core part of the nanofibers. The core/sheath magnetic composite nanofibers exhibited superparamagnetic behavior at room temperature and the magnetic nanoparticles in MRF well responded to an applied magnetic field. Also, the mechanical properties of the nanofiber were improved in the magnetic field. This study aimed to fabricate core/sheath magnetic composite nanofibers using coaxial electrospinning and characterize the magnetic as well as mechanical properties of composite nanofibers.

  15. Fibrinogen and fibrin based micro and nano scaffolds incorporated with drugs, proteins, cells and genes for therapeutic biomedical applications

    PubMed Central

    Rajangam, Thanavel; An, Seong Soo A

    2013-01-01

    Over the past two decades, many types of natural and synthetic polymer-based micro- and nanocarriers, with exciting properties and applications, have been developed for application in various types of tissue regeneration, including bone, cartilage, nerve, blood vessels, and skin. The development of suitable polymers scaffold designs to aid the repair of specific cell types have created diverse and important potentials in tissue restoration. Fibrinogen (Fbg)- and fibrin (Fbn)-based micro- and nanostructures can provide suitable natural matrix environments. Since these primary materials are abundantly available in blood as the main coagulation proteins, they can easily interact with damaged tissues and cells through native biochemical interactions. Fbg- and Fbn-based micro and nanostructures can also be consecutively furnished/or encapsulated and specifically delivered, with multiple growth factors, proteins, and stem cells, in structures designed to aid in specific phases of the tissue regeneration process. The present review has been carried out to demonstrate the progress made with micro and nanoscaffold applications and features a number of applications of Fbg- and Fbn-based carriers in the field of biomaterials, including the delivery of drugs, active biomolecules, cells, and genes, that have been effectively used in tissue engineering and regenerative medicine. PMID:24106425

  16. DNA-Based Enzyme Reactors and Systems

    PubMed Central

    Linko, Veikko; Nummelin, Sami; Aarnos, Laura; Tapio, Kosti; Toppari, J. Jussi; Kostiainen, Mauri A.

    2016-01-01

    During recent years, the possibility to create custom biocompatible nanoshapes using DNA as a building material has rapidly emerged. Further, these rationally designed DNA structures could be exploited in positioning pivotal molecules, such as enzymes, with nanometer-level precision. This feature could be used in the fabrication of artificial biochemical machinery that is able to mimic the complex reactions found in living cells. Currently, DNA-enzyme hybrids can be used to control (multi-enzyme) cascade reactions and to regulate the enzyme functions and the reaction pathways. Moreover, sophisticated DNA structures can be utilized in encapsulating active enzymes and delivering the molecular cargo into cells. In this review, we focus on the latest enzyme systems based on novel DNA nanostructures: enzyme reactors, regulatory devices and carriers that can find uses in various biotechnological and nanomedical applications. PMID:28335267

  17. Tunable Porosities and Shapes of Fullerene-Like Spheres

    PubMed Central

    Dielmann, Fabian; Fleischmann, Matthias; Heindl, Claudia; Peresypkina, Eugenia V; Virovets, Alexander V; Gschwind, Ruth M; Scheer, Manfred

    2015-01-01

    The formation of reversible switchable nanostructures monitored by solution and solid-state methods is still a challenge in supramolecular chemistry. By a comprehensive solid state and solution study we demonstrate the potential of the fivefold symmetrical building block of pentaphosphaferrocene in combination with CuI halides to switch between spheres of different porosity and shape. With increasing amount of CuX, the structures of the formed supramolecules change from incomplete to complete spherically shaped fullerene-like assemblies possessing an Ih-C80 topology at one side and to a tetrahedral-structured aggregate at the other. In the solid state, the formed nano-sized aggregates reach an outer diameter of 3.14 and 3.56 nm, respectively. This feature is used to reversibly encapsulate and release guest molecules in solution. PMID:25759976

  18. Computational design and multiscale modeling of a nanoactuator using DNA actuation.

    PubMed

    Hamdi, Mustapha

    2009-12-02

    Developments in the field of nanobiodevices coupling nanostructures and biological components are of great interest in medical nanorobotics. As the fundamentals of bio/non-bio interaction processes are still poorly understood in the design of these devices, design tools and multiscale dynamics modeling approaches are necessary at the fabrication pre-project stage. This paper proposes a new concept of optimized carbon nanotube based servomotor design for drug delivery and biomolecular transport applications. The design of an encapsulated DNA-multi-walled carbon nanotube actuator is prototyped using multiscale modeling. The system is parametrized by using a quantum level approach and characterized by using a molecular dynamics simulation. Based on the analysis of the simulation results, a servo nanoactuator using ionic current feedback is simulated and analyzed for application as a drug delivery carrier.

  19. Photonic monitoring of chitosan nanostructured alginate microcapsules for drug release

    NASA Astrophysics Data System (ADS)

    Khajuria, Deepak Kumar; Konnur, Manish C.; Vasireddi, Ramakrishna; Roy Mahapatra, D.

    2015-02-01

    By using a novel microfluidic set-up for drug screening applications, this study examines delivery of a novel risedronate based drug formulation for treatment of osteoporosis that was developed to overcome the usual shortcomings of risedronate, such as its low bioavailability and adverse gastric effects. Risedronate nanoparticles were prepared using muco-adhesive polymers such as chitosan as matrix for improving the intestinal cellular absorption of risedronate and also using a gastric-resistant polymer such as sodium alginate for reducing the gastric inflammation of risedronate. The in-vitro characteristics of the alginate encapsulated chitosan nanoparticles are investigated, including their stability, muco-adhesiveness, and Caco-2 cell permeability. Fluorescent markers are tagged with the polymers and their morphology within the microcapsules is imaged at various stages of drug release.

  20. Solid Lipid Nanoparticle-Based Calix[n]arenes and Calix-Resorcinarenes as Building Blocks: Synthesis, Formulation and Characterization

    PubMed Central

    Montasser, Imed; Shahgaldian, Patrick; Perret, Florent; Coleman, Anthony W.

    2013-01-01

    Solid lipid nanoparticles (SLNs) have attracted increasing attention during recent years. This paper presents an overview about the use of calix[n]arenes and calix-resorcinarenes in the formulation of SLNs. Because of their specific inclusion capability both in the intraparticle spaces and in the host cavities as well as their capacity for functionalization, these colloidal nanostructures represent excellent tools for the encapsulation of different active pharmaceutical ingredients (APIs) in the area of drug targeting, cosmetic additives, contrast agents, etc. Various synthetic routes to the supramolecular structures will be given. These various routes lead to the formulation of the corresponding SLNs. Characterization, properties, toxicological considerations as well as numerous corresponding experimental studies and analytical methods will be also exposed and discussed. PMID:24196356

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