gentamicins

Summary

Summary: A complex of three different closely related aminoglycoside sulfates, Gentamicins C1, C2, and C1(subA), obtained from Micromonospora purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit protein synthesis (GENETIC TRANSLATION).

Top Publications

  1. ncbi New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view
    Jose M Lopez-Novoa
    Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiologia y Farmacologia, Universidad de Salamanca, Salamanca, Spain
    Kidney Int 79:33-45. 2011
  2. pmc Aminoglycoside-induced histone deacetylation and hair cell death in the mouse cochlea
    Fu Quan Chen
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor, USA
    J Neurochem 108:1226-36. 2009
  3. ncbi Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats
    I Karahan
    Firat Universitesi, Veteriner Fakultesi, Farmakoloji ve Toksikoloji Anabilim Dali, 23119 Elazig, Turkey
    Toxicology 215:198-204. 2005
  4. ncbi Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy
    Vinod Malik
    Center for Gene Therapy, Research Institute at Nationwide Children s Hospital, Ohio State University, Columbus, OH 43205, USA
    Ann Neurol 67:771-80. 2010
  5. pmc Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system
    M Manuvakhova
    Department of Microbiology, The University of Alabama at Birmingham, 35294 2170, USA
    RNA 6:1044-55. 2000
  6. ncbi Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations
    Michael Wilschanski
    Department of Pediatrics, Cystic Fibrosis Center, Shaare Zedek Medical Center, Jerusalem, Israel
    N Engl J Med 349:1433-41. 2003
  7. pmc Vancomycin acts synergistically with gentamicin against penicillin-resistant pneumococci by increasing the intracellular penetration of gentamicin
    P Cottagnoud
    Department of Internal Medicine, Inselspital Bern, Bern, Switzerland
    Antimicrob Agents Chemother 47:144-7. 2003
  8. ncbi An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin
    Yaremi Quiros
    Departamento de Fisiologia y Farmacologia, Universidad de Salamanca, 37007 Salamanca, Spain
    Toxicol Sci 119:245-56. 2011
  9. pmc The human milk protein-lipid complex HAMLET sensitizes bacterial pathogens to traditional antimicrobial agents
    Laura R Marks
    Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, United States of America
    PLoS ONE 7:e43514. 2012
  10. ncbi Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modelling of a prospective study
    Elisabet I Nielsen
    Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
    Clin Pharmacokinet 48:253-63. 2009

Detail Information

Publications318 found, 100 shown here

  1. ncbi New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view
    Jose M Lopez-Novoa
    Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiologia y Farmacologia, Universidad de Salamanca, Salamanca, Spain
    Kidney Int 79:33-45. 2011
    ..Moreover, it discusses therapeutic perspectives for prevention of aminoglycoside nephrotoxicity derived from the pathophysiological knowledge...
  2. pmc Aminoglycoside-induced histone deacetylation and hair cell death in the mouse cochlea
    Fu Quan Chen
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor, USA
    J Neurochem 108:1226-36. 2009
    ..The results are consistent with an involvement of deficient histone acetylation in aminoglycoside-induced hair cell death and point to the potential value of HDAC-inhibitors in protection from the side effects of these drugs...
  3. ncbi Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats
    I Karahan
    Firat Universitesi, Veteriner Fakultesi, Farmakoloji ve Toksikoloji Anabilim Dali, 23119 Elazig, Turkey
    Toxicology 215:198-204. 2005
    ..It was concluded that lycopene as a novel natural antioxidant might have protective effects against gentamicin-induced nephrotoxicity and oxidative stress in rats...
  4. ncbi Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy
    Vinod Malik
    Center for Gene Therapy, Research Institute at Nationwide Children s Hospital, Ohio State University, Columbus, OH 43205, USA
    Ann Neurol 67:771-80. 2010
    ..Mutation suppression of stop codons, successfully achieved in the mdx mouse using gentamicin, represents an important evolving treatment strategy in Duchenne muscular dystrophy (DMD)...
  5. pmc Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system
    M Manuvakhova
    Department of Microbiology, The University of Alabama at Birmingham, 35294 2170, USA
    RNA 6:1044-55. 2000
    ..These results suggest that the mRNA context influences the suppression of stop codons in response to subtle differences in the conformation of the ribosomal decoding site that result from aminoglycoside binding...
  6. ncbi Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations
    Michael Wilschanski
    Department of Pediatrics, Cystic Fibrosis Center, Shaare Zedek Medical Center, Jerusalem, Israel
    N Engl J Med 349:1433-41. 2003
    ..We assessed whether topical administration of gentamicin to the nasal epithelium of patients with cystic fibrosis could result in the expression of functional CFTR channels...
  7. pmc Vancomycin acts synergistically with gentamicin against penicillin-resistant pneumococci by increasing the intracellular penetration of gentamicin
    P Cottagnoud
    Department of Internal Medicine, Inselspital Bern, Bern, Switzerland
    Antimicrob Agents Chemother 47:144-7. 2003
    ..These data suggest that the synergy observed in vivo and in vitro is based on an increased intracellular penetration of the aminoglycoside, probably due to the effect of vancomycin on the permeability of the cell wall...
  8. ncbi An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin
    Yaremi Quiros
    Departamento de Fisiologia y Farmacologia, Universidad de Salamanca, 37007 Salamanca, Spain
    Toxicol Sci 119:245-56. 2011
    ..The purpose of this review was to critically integrate all these effects and discuss their relative contribution to tubular cell death...
  9. pmc The human milk protein-lipid complex HAMLET sensitizes bacterial pathogens to traditional antimicrobial agents
    Laura R Marks
    Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, United States of America
    PLoS ONE 7:e43514. 2012
    ..Combined these results suggest the presence of a conserved HAMLET-activated pathway that circumvents antibiotic resistance in bacteria. The ability to activate this pathway may extend the lifetime of the current treatment arsenal...
  10. ncbi Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modelling of a prospective study
    Elisabet I Nielsen
    Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
    Clin Pharmacokinet 48:253-63. 2009
    ..A secondary aim was to evaluate cystatin C as a marker for gentamicin clearance in this patient population...
  11. ncbi Comparison of the course of biomarker changes and kidney injury in a rat model of drug-induced acute kidney injury
    Daisuke Sasaki
    Drug Safety Research Labs, Astellas Pharma Inc, Kashima, Yodogawa ku, Osaka, Japan
    Biomarkers 16:553-66. 2011
    ..To aid in evaluating the performance of biomarkers, we measured kidney injury biomarkers in rat models of drug-induced acute kidney injury...
  12. pmc Uptake of gentamicin by bullfrog saccular hair cells in vitro
    P S Steyger
    Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR 97201, USA
    J Assoc Res Otolaryngol 4:565-78. 2003
    ..Thus, GTTR is a valid fluorescent probe with which to investigate the pharmacokinetics and mechanisms of gentamicin accumulation...
  13. ncbi Tetramethylpyrazine protects rat renal tubular cell apoptosis induced by gentamicin
    Shu Hui Juan
    Department of Physiology, Taipei Medical University, Taipei, Taiwan
    Nephrol Dial Transplant 22:732-9. 2007
    ..Tetramethylpyrazine (TMP) is a compound purified from the rhizome of Ligusticum wallichi (Chuanxiong) and has been found to protect against ischaemia-reperfusion injury, nephritis and alcohol-induced toxicity in rat kidneys...
  14. ncbi Antioxidant S-allylcysteine prevents gentamicin-induced oxidative stress and renal damage
    Perla D Maldonado
    Department of Biology, Universidad Nocional Autonoma de Mexico, Mexico D F, Mexico
    Free Radic Biol Med 35:317-24. 2003
    ..In conclusion, SAC ameliorates the GM-induced ARF by a mechanism related, at least in part, to its ability to decrease oxidative stress and to preserve antioxidant enzymes activity in renal cortex...
  15. ncbi Agents ameliorating or augmenting experimental gentamicin nephrotoxicity: some recent research
    B H Ali
    Department of Veterinary Medicine, King Saud University, PO Box 10158 Buraydah, Al Gaseem 81999, Saudi Arabia
    Food Chem Toxicol 41:1447-52. 2003
    ..g. garlic). Other ameliorating agents include antibiotics (e.g. ceftriaxone), antiplatelet drugs (e.g. trapidil) and Ca++ agents that may augment GM nephrotoxicity include cyclosporin and the Ca++-channel blocker verapamil...
  16. pmc Trafficking of systemic fluorescent gentamicin into the cochlea and hair cells
    Qi Wang
    Oregon Hearing Research Center, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    J Assoc Res Otolaryngol 10:205-19. 2009
    ..Trans-strial trafficking of aminoglycosides from strial capillaries to marginal cells will be dependent on as-yet-unidentified mechanisms that convey these drugs across the intra-strial electrical barrier and into marginal cells...
  17. ncbi Garlic ameliorates gentamicin nephrotoxicity: relation to antioxidant enzymes
    J Pedraza-Chaverri
    Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico UNAM, 04510, Distrito Federal, Mexico
    Free Radic Biol Med 29:602-11. 2000
    ..CAT mRNA levels decreased in the GM group. The protective effect of garlic is associated with the prevention of the decrease of Mn-SOD and GPx activities and with the rise of lipoperoxidation in renal cortex...
  18. ncbi Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats
    Srinivasan Kalayarasan
    Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India
    Eur J Pharmacol 606:162-71. 2009
    ..To conclude, DAS enhances antioxidants and suppresses inflammatory cytokines through the activation of Nrf2, thereby protecting the cell against oxidative stress induced by gentamicin...
  19. ncbi Integrated pathway analysis of rat urine metabolic profiles and kidney transcriptomic profiles to elucidate the systems toxicology of model nephrotoxicants
    Ethan Yixun Xu
    Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Chem Res Toxicol 21:1548-61. 2008
    ..Furthermore, this analysis suggests that renal transcription factors HNF1alpha, HNF1beta, and HIF-1 might be the central mediators of drug-induced kidney injury and adaptive response pathways...
  20. ncbi Apoptotic death of hair cells in mammalian vestibular sensory epithelia
    A Forge
    Institute of Laryngology and Otology, University College London, 330 332 Gray s Inn Road, London, UK
    Hear Res 139:97-115. 2000
    ..Explant cultures of mature vestibular organs may be, therefore, a useful model system for examining putative hair cell protecting agents...
  21. ncbi Premature stop codons involved in muscular dystrophies show a broad spectrum of readthrough efficiencies in response to gentamicin treatment
    L Bidou
    1CNRS UMR 8621, Institut de Genetique et Microbiologie, Universite Paris Sud, Orsay Cedex, France
    Gene Ther 11:619-27. 2004
    ....
  22. pmc Acoustic trauma increases cochlear and hair cell uptake of gentamicin
    Hongzhe Li
    Department of Otolaryngology Head and Neck Surgery, Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon, United States of America
    PLoS ONE 6:e19130. 2011
    ..In this study, we tested the hypothesis that sound exposure enhances the intra-cochlear trafficking of aminoglycosides, such as gentamicin, leading to increased hair cell uptake of aminoglycosides and subsequent ototoxicity...
  23. pmc Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo
    Konstantinos Anagnostakos
    Klinik fur Orthopadie und Orthopadische Chirurgie, Universitat des Saarlandes, Homburg Saar, Germany
    Acta Orthop 80:193-7. 2009
    ..However, little is known about antibiotic elution from bone cement beyond the first 2-3 postoperative days in humans...
  24. ncbi Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus
    Vance G Fowler
    Duke University Medical Center, Durham, NC 27710, USA
    N Engl J Med 355:653-65. 2006
    ..Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed...
  25. ncbi Comparative analysis of novel noninvasive renal biomarkers and metabonomic changes in a rat model of gentamicin nephrotoxicity
    Max Sieber
    Department of Toxicology, University of Wurzburg, 97078 Wurzburg, Germany
    Toxicol Sci 109:336-49. 2009
    ..The early increase in urine, which correlated with enhanced gene and protein expression at the site of injury, provides further support for lipocalin-2 and Kim-1 as sensitive, noninvasive biomarkers of nephrotoxicity...
  26. ncbi Hair cell recovery in the vestibular sensory epithelia of mature guinea pigs
    A Forge
    Institute of Laryngology and Otology, University College London, United Kingdom
    J Comp Neurol 397:69-88. 1998
    ..There was also no evidence of any hair cell recovery in the organ of Corti. Thus, there appear to be limitations on the capacity for spontaneous replacement of lost hair cells in the mammalian inner ear...
  27. ncbi Hair cell regeneration in sensory epithelia from the inner ear of a urodele amphibian
    Ruth R Taylor
    UCL Centre for Auditory Research, University College London, London WC1X 8EE, United Kingdom
    J Comp Neurol 484:105-20. 2005
    ..A similar mechanism has been proposed for the hair cell recovery phenomenon observed in the vestibular organs of mammals...
  28. ncbi Leishmania major H-line attenuated under pressure of gentamicin, induces a Th1 response which protects susceptible BALB/c mice against infection with virulent L. major
    Hamid Daneshvar
    Medical School, University of Kerman, Kerman, Iran
    Parasitology 136:1243-50. 2009
    ..Mice infected with L. major H-line acquired some resistance against L. major WT. These results show that the attenuated cell line of L. major is not only avirulent but that it may also modulate the host immune response...
  29. ncbi Effects of systemic versus local gentamicin on the inner ear in the Atlantic cod, Gadus morhua (L.), relevance for fish hearing investigations
    K Faucher
    ENT Department, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway
    Hear Res 240:12-21. 2008
    ..Here, we observed decreased hair cell density, high prevalence of immature hair cells, and significantly shortened kinocilia...
  30. ncbi Improvement of gentamicin poly(D,L-lactic-co-glycolic acid) microspheres for treatment of osteomyelitis induced by orthopedic procedures
    Maria Rosa Virto
    Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid 28040, Spain
    Biomaterials 28:877-85. 2007
    ..Two models, one of them including an autocatalytic process, were finally proposed to contribute to understand the mass transport mechanism involved in drug release from these microspheres...
  31. pmc The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk
    Denis N Silachev
    A N Belozersky Institute of Physico Chemical Biology, Lomonosov Moscow State University, Moscow, Russia
    PLoS ONE 7:e51553. 2012
    ....
  32. ncbi Melatonin protects against gentamicin-induced nephrotoxicity in rats
    Goksel Sener
    Department of Pharmacology, School of Pharmacy, Marmara University, Istanbul, Turkey
    J Pineal Res 32:231-6. 2002
    ..On the other hand simultaneous melatonin administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GEN treatment...
  33. ncbi Collagen as a carrier for on-site delivery of antibacterial drugs
    Zbigniew Ruszczak
    INNOCOLL GmbH, Saal, Germany
    Adv Drug Deliv Rev 55:1679-98. 2003
    ..Recent efforts in the use of collagen and collagen-synthetic polymer composites for controlled drug delivery as well as collagen-based diffusion membranes for prolonged drug release have also been included in this review...
  34. ncbi Aged garlic extract attenuates gentamicin induced renal damage and oxidative stress in rats
    Perla D Maldonado
    Department of Biology, Faculty of Chemistry, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, 04510 D F, Mexico, Mexico
    Life Sci 73:2543-56. 2003
    ..These data suggest that AGE may be a useful agent for the prevention of GM-nephrotoxicity...
  35. ncbi Protective role of caffeic acid phenethyl ester (cape) on gentamicin-induced acute renal toxicity in rats
    H Parlakpinar
    Department of Pharmacology, Faculty of Medicine, Inonu University, 44280 Malatya, Turkey
    Toxicology 207:169-77. 2005
    ..Our results indicated that CAPE acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN both at the biochemical and histological level. Thus, CAPE could be effectively combined with GEN treatment...
  36. ncbi Stop-codon read-through for patients affected by a lysosomal storage disorder
    Doug A Brooks
    Lysosomal Diseases Research Unit, Department of Genetic Medicine, Children Youth and Women s Health Service, 72 King William Rd, North Adelaide, South Australia 5006, Australia
    Trends Mol Med 12:367-73. 2006
    ....
  37. ncbi A role for superoxide in gentamicin-mediated nephropathy in rats
    Salvatore Cuzzocrea
    Institute of Pharmacology, University of Messina, Torre Biologica Policlinico Universitario, Via C Valeria Gazzi, 98100 Messina, Italy
    Eur J Pharmacol 450:67-76. 2002
    ....
  38. ncbi Prophylaxis and treatment of implant-related infections by local application of antibiotics
    Michael Diefenbeck
    Klinik fur Unfall und Wiederherstellungschirurgie, Berufsgenossenschaftliche Kliniken Bergmannstrost, Halle Saale, Germany
    Injury 37:S95-104. 2006
    ..The second part discusses the role of local antibiotics such as gentamicin PMMA beads, and gentamicin-collagen and antibiotic-loaded cement spacers in treating implant-related infections...
  39. pmc Influence of extracellular bactericidal agents on bacteria within macrophages
    Terri S Hamrick
    Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA
    Infect Immun 71:1016-9. 2003
    ....
  40. ncbi Gentamicin-attenuated Leishmania infantum: cellular immunity production and protection of dogs against experimental canine leishmaniasis
    H Daneshvar
    Medical School, University of Kerman, Iran
    Parasite Immunol 32:722-30. 2010
    ..infantum H-line i.d. 12 months previously were protected against challenge with L. infantum WT. These data suggest that the L. infantum H-line was safe and induced a protection which is correlated with cellular immunity in dogs...
  41. pmc Apoptosis in renal proximal tubules of rats treated with low doses of aminoglycosides
    M El Mouedden
    Unités de Pharmacologie Cellulaire et Moléculaire, Belgium
    Antimicrob Agents Chemother 44:665-75. 2000
    ..Whereas a relation between aminoglycoside-induced tubular apoptosis and cortical proliferative response seems to be established, no simple correlation with phospholipidosis can be drawn...
  42. ncbi Clinical doses of amikacin provide more effective suppression of the human CFTR-G542X stop mutation than gentamicin in a transgenic CF mouse model
    Ming Du
    Department of Microbiology, The University of Alabama at Birmingham, 35294 2170, USA
    J Mol Med (Berl) 84:573-82. 2006
    ..Because amikacin is also less toxic than gentamicin, it may represent a superior choice for suppression therapy in patients that carry a premature stop mutation in the CFTR gene...
  43. pmc Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin
    Liat Linde
    Department of Genetics, Life Sciences Institute, The Hebrew University of Jerusalem, Jerusalem, Israel
    J Clin Invest 117:683-92. 2007
    ..Together our results suggest that the efficiency of NMD might vary and hence have an important role in governing the response to treatments aiming to promote readthrough of PTCs in many genetic diseases...
  44. ncbi Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway
    Ana I Morales
    Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain
    Kidney Int 77:861-9. 2010
    ..Thus, our study suggests that pleiotropic effects of metformin can lessen gentamicin nephrotoxicity and improve mitochondrial homeostasis...
  45. ncbi Gentamicin is ototoxic to all hair cells in the fish lateral line system
    William J Van Trump
    Department of Ecology and Evolutionary Biology, 321 Steinhaus Hall, University of California, Irvine, CA 92697, USA
    Hear Res 261:42-50. 2010
    ..These findings argue for a re-evaluation of the results of studies that have used gentamicin to differentiate the roles of the two classes of neuromast in fish behavior...
  46. ncbi Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death
    Reese H Clark
    Pediatrix Obstetrix Center for Research and Education, Sunrise, Florida, USA
    Pediatrics 117:67-74. 2006
    ..As a result, we recommended that ampicillin and gentamicin be used as empiric coverage for early-onset neonatal sepsis while culture results are awaited...
  47. ncbi Damage and functional recovery of the Atlantic cod (Gadus morhua) inner ear hair cells following local injection of gentamicin
    Karine Faucher
    ENT Department, Institute of Clinical Medicine, University of Tromsø, Norway
    Int J Audiol 48:456-64. 2009
    ..These observations suggest that the macula sacculi of Atlantic cod can regenerate towards a near-complete functional and ultrastructural recovery within 17-21 days following ototoxic gentamicin treatment...
  48. ncbi Population pharmacokinetics of gentamicin in premature newborns
    Benito García
    Pharmacy Service, Hospital Severo Ochoa Leganes, and Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University Complutense of Madrid, Spain
    J Antimicrob Chemother 58:372-9. 2006
    ..To validate the pharmacokinetic analysis performed in another population of 50 premature newborns...
  49. ncbi Antibacterial efficacy of a new gentamicin-coating for cementless prostheses compared to gentamicin-loaded bone cement
    Danielle Neut
    Department of Biomedical Engineering, University Medical Center Groningen, The Netherlands
    J Orthop Res 29:1654-61. 2011
    ....
  50. ncbi Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation
    H Servais
    Faculty of Medicine, Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain UCL 7370, Avenue E Mounier 73, Brussels, Belgium
    Apoptosis 13:11-32. 2008
    ..Finally, key issues that need to be addressed for the success of apoptosis-based therapies are underlined...
  51. pmc Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations
    Igor Nudelman
    The Edith and Joseph Fischer Enzyme Inhibitors Laboratory, Schulich Faculty of Chemistry, Technion Israel Institute of Technology, Haifa 32000, Israel
    J Med Chem 52:2836-45. 2009
    ..Comparative acute lethal toxicity in mice, cell toxicity, and the assessment of hair cell toxicity in cochlear explants further indicated that 2 exhibits far lower toxicity than that of gentamicin...
  52. ncbi Molecular cloning of the fish interferon stimulated gene, 15 kDa (ISG15) orthologue: a ubiquitin-like gene induced by nephrotoxic damage
    Mingjuan Liu
    Molecular and Cellular Biology Program, University of Maryland Baltimore, 108 N Greene Street, Baltimore, MD 21201, USA
    Gene 298:129-39. 2002
    ....
  53. pmc Mechanisms of rapid sensory hair-cell death following co-administration of gentamicin and ethacrynic acid
    Dalian Ding
    Center for Hearing and Deafness, Dept of Communicative Disorders and Sciences, 137 Cary Hall, University at Buffalo, Buffalo, NY 14214, USA
    Hear Res 259:16-23. 2010
    ....
  54. ncbi Biological qualification of biomarkers of chemical-induced renal toxicity in two strains of male rat
    Ernie Harpur
    Sanofi Aventis, Alnwick, Northumberland, UK
    Toxicol Sci 122:235-52. 2011
    ..Qualification of α-GST must await further explanation of the differences in response to PT and CD injury...
  55. pmc The microbiology of the infected knee arthroplasty
    R S J Nickinson
    Centre for Hip Surgery, Wrightington Hospital, Wrightington, Wigan and Leigh NHS Trust, Appley Bridge, Wigan, Lancashire, UK
    Int Orthop 34:505-10. 2010
    ..Gentamicin combined with vancomycin offers the most comprehensive protection and potentially allows for infected knee arthoplasties to be treated with a one-stage procedure...
  56. ncbi Role of myofibroblasts, macrophages, transforming growth factor-beta endothelin, angiotensin-II, and fibronectin in the progression of tubulointerstitial nephritis induced by gentamicin
    Tufik J Geleilete
    Department of Internal Medicine, Faculty of Medicine, Ribeirao Preto, SP, Brazil
    J Nephrol 15:633-42. 2002
    ....
  57. ncbi Novel biodegradable composite wound dressings with controlled release of antibiotics: results in a guinea pig burn model
    Jonathan J Elsner
    Dept of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel
    Burns 37:896-904. 2011
    ..The current dressing material exhibits promising results, does not require frequent bandage changes, and offers a potentially valuable and economic approach to treating the life-threatening complication of burn-related infections...
  58. ncbi Increased expression of p38 mitogen-activated protein kinase is related to the acute renal lesions induced by gentamicin
    R A Volpini
    Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Ribeirao Preto, SP, Brasil
    Braz J Med Biol Res 39:817-23. 2006
    ..The increased expression of p-p38 MAPK and NF-kappaB observed in these rats suggests that these signaling molecules may be involved in the pathogenesis of tubulointerstitial nephritis induced by gentamicin...
  59. ncbi A prospective, randomized, double-blind studyof single high dose versus multiple standard dose gentamicin both in combination withmetronidazole for colorectal surgicalprophylaxis
    S A Zelenitsky
    Departments of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada
    J Hosp Infect 46:135-40. 2000
    ..2% (6/27) vs. 55% (11/20), respectively (P= 0.021). Single high dose gentamicin plus metronidazole preoperatively was at least as effective as the multiple standard dose regimen and may be more effective for prolonged operations...
  60. pmc Gentamicin causes apoptosis at low concentrations in renal LLC-PK1 cells subjected to electroporation
    Hélène Servais
    Unité de Pharmacologie Cellulaire et Moléculaire, Universite Catholique de Louvain, 7370 avenue E Mounier 73, B 1200 Brussels, Belgium
    Antimicrob Agents Chemother 50:1213-21. 2006
    ..The data indicate that cytosolic gentamicin triggers apoptosis. Sequestration of gentamicin in lysosomes would, to some extent, protect against apoptosis...
  61. pmc Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin
    Tanja Matt
    Institut fur Medizinische Mikrobiologie, Universitat Zurich, 8006 Zurich, Switzerland
    Proc Natl Acad Sci U S A 109:10984-9. 2012
    ..Together with 3D structures of apramycin-ribosome complexes at 3.5-Å resolution, our results provide a conceptual framework for further development of less toxic aminoglycosides by hypothesis-driven chemical synthesis...
  62. pmc Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo
    C F Dai
    Oregon Hearing Research Center, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Hear Res 213:64-78. 2006
    ..GTTR uptake by hair cells in vivo suggests that GTTR has potential to elucidate aminoglycoside transport mechanisms into the inner ear, and as a bio-tracer for in vivo pharmacokinetic studies...
  63. ncbi Preparation of aminoglycoside-loaded chitosan nanoparticles using dextran sulphate as a counterion
    Enxian Lu
    Department of Biopharmaceutical Science, University of Illinois at Chicago, IL, USA
    J Microencapsul 26:346-54. 2009
    ....
  64. ncbi Possible involvement of erythropoietin in remote renal preconditioning-induced cardioprotection in rats
    Vishal Diwan
    Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Punjab, India
    J Cardiovasc Pharmacol 51:126-30. 2008
    ..These results implicate that RRPC-induced cardioprotective effects may be mediated through release of erythropoietin from kidney...
  65. ncbi Differential ablation of sensory receptors underlies ototoxin-induced shifts in auditory thresholds of the goldfish (Carassius auratus)
    John Ramcharitar
    St Mary s College of Maryland, Department of Biology, 18952 E Fisher Road, St Mary s City, MD 20686, USA
    J Appl Toxicol 30:536-41. 2010
    ..We propose that fish auditory systems should be used alongside the lateral line, for the assessment of ototoxicity in new-developed drugs...
  66. pmc An antibiotic selection marker for schistosome transgenesis
    Gabriel Rinaldi
    Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, 2300 I Street NW, Washington, DC 20037, USA
    Int J Parasitol 42:123-30. 2012
    ..The availability of antibiotic selection can be expected to enhance progress with functional genomics research on the helminth parasites responsible for major neglected tropical diseases...
  67. pmc Cytoplasmic and intra-nuclear binding of gentamicin does not require endocytosis
    Sigrid E Myrdal
    Oregon Hearing Research Center, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Hear Res 204:156-69. 2005
    ....
  68. ncbi Repairing faulty genes by aminoglycosides: development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations
    Igor Nudelman
    The Edith and Joseph Fischer Enzyme Inhibitors Laboratory, Technion Israel Institute of Technology, Haifa 32000, Israel
    Bioorg Med Chem 18:3735-46. 2010
    ..The superiority of new leads was demonstrated in six different nonsense DNA-constructs underling the genetic diseases cystic fibrosis, Duchenne muscular dystrophy, Usher syndrome and Hurler syndrome...
  69. ncbi In vitro-in vivo characterization of gentamicin bone implants
    M Baro
    Servicio de Traumatologia, Hospitén Rambla S L, Santa Cruz de Tenerife, Spain
    J Control Release 83:353-64. 2002
    ..Gentamicin concentration in the areas of the bone closest to the implant was higher than the minimum inhibitory concentration (MIC) against Staphylococcus aureus...
  70. ncbi Drug-induced readthrough of premature stop codons leads to the stabilization of laminin alpha2 chain mRNA in CMD myotubes
    Valérie Allamand
    INSERM, U582, Paris, France
    J Gene Med 10:217-24. 2008
    ..A promising approach for the treatment of genetic disorders due to premature termination codons (PTCs) is the use of drugs to force stop codon readthrough...
  71. ncbi Suppression of nonsense mutations in Rett syndrome by aminoglycoside antibiotics
    Cornelia Brendel
    Department of Pediatrics and Pediatric Neurology, Georg August University, Gottingen, D 37075 Germany
    Pediatr Res 65:520-3. 2009
    ..We have shown that aminoglycoside-mediated read-through of nonsense mutations in the MECP2 gene can be achieved in vitro with efficiency comparable with that seen in other disorders...
  72. ncbi Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements
    H van de Belt
    Department of Orthopedic Surgery, University Hospital, Groningen, The Netherlands
    Biomaterials 22:1607-11. 2001
    ..Summarising, this study demonstrates that although gentamicin loading of bone cements yields reductions in biofilm formation, S. aureus is able to grow on gentamicin-loaded bone cements...
  73. ncbi Leupeptin protects cochlear and vestibular hair cells from gentamicin ototoxicity
    Dalian Ding
    Hearing Research Lab, 215 Parker Hall, SUNY University at Buffalo, NY 14214, USA
    Hear Res 164:115-26. 2002
    ..1 and 3 mM. These results suggest that one of the early steps in GM ototoxicity may involve calcium-activated proteases that lead to the demise of cochlear and vestibular hair cells...
  74. pmc Functional hair cell mechanotransducer channels are required for aminoglycoside ototoxicity
    Abdelrahman Alharazneh
    Department of Otolaryngology Head and Neck Surgery, Stanford University, Stanford, California, United States of America
    PLoS ONE 6:e22347. 2011
    ..Results suggest that limiting permeation of AGs through MET channel or preventing their entry into endolymph are potential therapeutic targets for preventing hair cell death and hearing loss...
  75. ncbi Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats
    M Lucke
    Department of Trauma and Reconstructive Surgery, Charite, Humboldt University of Berlin, Germany
    Bone 32:521-31. 2003
    ..Local application of antibiotic-coated orthopedic devices containing PDLLA and 10% gentamicin significantly reduced implant-related infection in this animal model...
  76. pmc Molecular characterization of gentamicin-resistant Enterococci in the United States: evidence of spread from animals to humans through food
    S M Donabedian
    Division of Infectious Disease, Department of Medicine, William Beaumont Hospital, Royal Oak, Detroit, Michigan 48073, USA
    J Clin Microbiol 41:1109-13. 2003
    ....
  77. ncbi Bacteriophage versus antimicrobial agents for the treatment of murine burn wound infection caused by Klebsiella pneumoniae B5055
    Seema Kumari
    Basic Medical Sciences Building, Department of Microbiology, Panjab University, Chandigarh 160014, India
    J Med Microbiol 60:205-10. 2011
    ..pneumoniae B5055 in comparison to multiple applications of silver nitrate and gentamicin...
  78. ncbi The use of zebrafish for assessing ototoxic and otoprotective agents
    Christopher Ton
    Phylonix Pharmaceuticals, Inc, 100 Inman St, Cambridge, MA 02139, USA
    Hear Res 208:79-88. 2005
    ..Our data indicate that results of ototoxicity and otoprotection in zebrafish correlated with results in humans, supporting use of zebrafish for preliminary drug screening...
  79. pmc WR279,396, a third generation aminoglycoside ointment for the treatment of Leishmania major cutaneous leishmaniasis: a phase 2, randomized, double blind, placebo controlled study
    Afif Ben Salah
    Institut Pasteur de Tunis, Tunis, Tunisia
    PLoS Negl Trop Dis 3:e432. 2009
    ..Accordingly, the treatment of CL with WR279,396, a formulation of paromomycin and gentamicin in a hydrophilic base, was investigated in a phase 2 clinical study in Tunisia and France...
  80. pmc In vitro readthrough of termination codons by gentamycin in the Stüve-Wiedemann Syndrome
    Samuel Bellais
    Département de génétique, Universite Paris Descartes, INSERM U781, Assistance Publique Hôitaux de Paris, Hopital Necker Enfants Malades, Paris, France
    Eur J Hum Genet 18:130-2. 2010
    ....
  81. pmc No detectable improvements in cystic fibrosis transmembrane conductance regulator by nasal aminoglycosides in patients with cystic fibrosis with stop mutations
    John P Clancy
    Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Avenue South, Birmingham, AL 35233, USA
    Am J Respir Cell Mol Biol 37:57-66. 2007
    ..The study provides valuable information on parameters of the nasal potential difference measurements for use in future multicenter clinical trials...
  82. ncbi Extracellular divalent cations modulate aminoglycoside-induced hair cell death in the zebrafish lateral line
    Allison B Coffin
    Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology Head and Neck Surgery, University of Washington, Box 357923, Seattle, WA 98195, USA
    Hear Res 253:42-51. 2009
    ..These experiments lend further support to the hypothesis that aminoglycoside toxicity occurs via multiple pathways in a both a drug and time course-specific manner...
  83. ncbi Protective effect of green tea extract on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney
    Sara A Khan
    Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, U P, India
    Pharmacol Res 59:254-62. 2009
    ..In conclusion, green tea ameliorates GM elicited nephrotoxicity and oxidative damage by improving antioxidant defense, tissue integrity and energy metabolism...
  84. pmc Response of mechanosensory hair cells of the zebrafish lateral line to aminoglycosides reveals distinct cell death pathways
    Kelly N Owens
    Department of Biological Structure, V M Bloedel Hearing Research Center, University of Washington, Box 357420, Seattle, WA 98195 7420, USA
    Hear Res 253:32-41. 2009
    ..The distinctions between the times of action of these aminoglycosides indicate that these drugs induce multiple cell death pathways...
  85. pmc TRPV4 enhances the cellular uptake of aminoglycoside antibiotics
    Takatoshi Karasawa
    Oregon Hearing Research Center, Oregon Health and Science University, 3181 Sam Jackson Park Road, Portland, OR 97239, USA
    J Cell Sci 121:2871-9. 2008
    ..In an endolymph-like extracellular environment, clearance of GTTR was attenuated from KPT2-TRPV4 cells in a TRPV4-dependent fashion. We propose that TRPV4 has a role in aminoglycoside uptake and retention in the cochlea...
  86. ncbi Gentamicin-induced apoptosis in LLC-PK1 cells: involvement of lysosomes and mitochondria
    Hélène Servais
    Unité de Pharmacologie Cellulaire et Moléculaire, Universite Catholique de Louvain, UCL 73 70 Avenue E Mounier 73, B 1200 Brussels, Belgium
    Toxicol Appl Pharmacol 206:321-33. 2005
    ..The present data provide temporal evidence that gentamicin causes apoptosis in LLC-PK1 with successive alteration of the permeability of lysosomes, triggering of the mitochondrial pathway, and activation of caspase-3...
  87. ncbi Brucellar spondylitis: review of 35 cases and literature survey
    J Solera
    Department of Internal Medicine, Hospital General de Albacete, 02006 Albacete, Spain
    Clin Infect Dis 29:1440-9. 1999
    ..There were no deaths or severe sequelae in this study. Brucellar spondylitis causes considerable suffering and absenteeism from work, but long-term clinical responses are favorable...
  88. pmc Restoration of W1282X CFTR activity by enhanced expression
    Steven M Rowe
    Department of Medicine, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294 0006, USA
    Am J Respir Cell Mol Biol 37:347-56. 2007
    ..These findings provide evidence that W1282X CFTR exhibits membrane localization and retained chloride channel function after enhanced expression, and suggest that patients harboring this mutation may be more susceptible to CFTR rescue...
  89. ncbi Progression of hair cell ejection and molecular markers of apoptosis in the avian cochlea following gentamicin treatment
    Dominic A Mangiardi
    Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
    J Comp Neurol 475:1-18. 2004
    ....
  90. pmc Activity of daptomycin alone and in combination with rifampin and gentamicin against Staphylococcus aureus assessed by time-kill methodology
    Kim Credito
    Department of Pathology, Hershey Medical Center, P O Box 850, Hershey, PA 17033, USA
    Antimicrob Agents Chemother 51:1504-7. 2007
    ..Daptomycin combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus strain only, and virtually all synergy occurred between daptomycin and gentamicin...
  91. ncbi Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review
    Gerhard Schmidmaier
    Centrum für Muskuloskeletale Chirurgie, Charite Universitatsmedizin Berlin, Germany
    Injury 37:S105-12. 2006
    ..So far, the results suggest that a local application of gentamicin from PDLLA-coated implants might support systemic antibiotic prophylaxis in preventing implant-associated osteomyelitis...
  92. pmc Antibiotic pharmacodynamics in surgical prophylaxis: an association between intraoperative antibiotic concentrations and efficacy
    Sheryl A Zelenitsky
    Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada
    Antimicrob Agents Chemother 46:3026-30. 2002
    ....
  93. ncbi Choice of antibiotics for infection prophylaxis in emergency cesarean sections in low-income countries: a cost-benefit study in Mozambique
    Vicente Kayihura
    Department of Obstetrics and Gynecology, Maputo Central Hospital, Maputo, Mozambique
    Acta Obstet Gynecol Scand 82:636-41. 2003
    ..There is a need to assess the cost-benefit of different models of antibiotic administration for the prevention of post cesarean infection, particularly in resource-scarce settings...
  94. pmc Synergistic ototoxicity due to noise exposure and aminoglycoside antibiotics
    Hongzhe Li
    Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon, USA
    Noise Health 11:26-32. 2009
    ..Preventing the ototoxic synergy of noise and aminoglycosides is best achieved by using non-ototoxic bactericidal drugs, and by attenuating perceived noise intensity when life-saving aminoglycoside therapy is required...
  95. ncbi Protective effects of alpha-tocopherol against gentamicin-induced Oto-vestibulo toxicity: an experimental study
    Anna Rita Fetoni
    Institute of Otolaryngology, Catholic University of Rome, Rome, Italy
    Acta Otolaryngol 123:192-7. 2003
    ....
  96. pmc Production of beta-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous beta(0)39 thalassemia patients
    Francesca Salvatori
    BioPharmaNet, Department of Biochemistry and Molecular Biology, Ferrara University, Ferrara, Italy
    Am J Hematol 84:720-8. 2009
    ..Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc...
  97. ncbi Beneficial read-through of a USH1C nonsense mutation by designed aminoglycoside NB30 in the retina
    Tobias Goldmann
    Institute of Zoology, Department of Cell and Matrix Biology, Johannes Gutenberg University of Mainz, Mainz, Germany
    Invest Ophthalmol Vis Sci 51:6671-80. 2010
    ..Here, we investigated the capability of the novel synthetic aminoglycoside NB30 for the translational read-through of the USH1C-p.R31X nonsense mutation as a retinal therapy option...
  98. ncbi Megalin deficiency offers protection from renal aminoglycoside accumulation
    Christian Schmitz
    Max Delbrueck Center for Molecular Medicine, Berlin D 13125, Germany
    J Biol Chem 277:618-22. 2002
    ....
  99. ncbi Exogenous control of mammalian gene expression via modulation of translational termination
    George J Murphy
    Department of Genetics, Harvard Medical School, and Division of Molecular Medicine, Children s Hospital, Boston, Massachusetts 02115, USA
    Nat Med 12:1093-9. 2006
    ..This gene regulation strategy offers significant advantages over existing methods for controlling gene expression and should have both immediate experimental application and possible clinical application...
  100. pmc Distribution of gentamicin in the guinea pig inner ear after local or systemic application
    Shun ichi Imamura
    Department of Otolaryngology, Shinshu University School of Medicine, 3 1 1 Asahi, Matsumoto, Nagano 390 8621, Japan
    J Assoc Res Otolaryngol 4:176-95. 2003
    ....
  101. ncbi Antibacterial activity of liposomal gentamicin against Pseudomonas aeruginosa: a time-kill study
    Gavin Rukholm
    The Novel Drug and Vaccine Delivery Systems Facility, Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Road, Sudbury, Ont, Canada P3E 2C6
    Int J Antimicrob Agents 27:247-52. 2006
    ..In conclusion, our liposomal gentamicin formulation is a more potent antipseudomonal drug with an improved killing time and prolonged antimicrobial activity...

Research Grants64

  1. Mechanisms of Cochlear Oxidative Stress Injury and Strategies to Protect Hearing
    Michael J Brenner; Fiscal Year: 2013
    ..The long-term goal of this research is to develop safe and effective strategies to prevent hearing loss related to aminoglycoside antibiotic therapy. ..
  2. A Novel Drug for Septicemia Targets A1 ARs
    Constance Neely Wilson; Fiscal Year: 2010
    ..Thus, there is a large unmet medical need for a safe, effective anti-sepsis therapy which can be used as an adjunctive therapy to antibiotics for the treatment of sepsis. ..
  3. Bacterial Stress Responses to Intestinal Inflammation
    JONATHAN JAMES HANSEN; Fiscal Year: 2013
    ....
  4. Three-dimensional Human Kidney Tissue System for Studying Renal Diseases
    Jeannine Coburn; Fiscal Year: 2013
    ..Furthermore, the model can be extended to the engineering of other organs further broadening its applications. ..
  5. Mechanistic Basis Underlying Protein Repair of CFTR Nonsense Mutations
    STEVEN MARK ROWE; Fiscal Year: 2010
    ....
  6. Hemostatic-antibiotic Combination for Prevention of MRSA Surgical Site Infections
    Timothy C Fisher; Fiscal Year: 2010
    ..g., thrombin, collagen, fibrin). Thus, once developed and proven effective for SWI prevention, the Ostene+ Gentamicin combination would be not expected to meet any major barrier to acceptance. ..
  7. Identification of gentamicin-binding proteins in the inner ear
    Takatoshi Karasawa; Fiscal Year: 2010
    ..These strategies will lead to ototoxicity and deafness prevention. ..
  8. Electrical Stimulation to Restore Three Dimensional Vestibular Sensation
    Charles C Della Santina; Fiscal Year: 2012
    ....
  9. Impact of endogenous metabolic biases on ototoxic oxidative damage
    HEATHER COLLEEN JENSEN SMITH; Fiscal Year: 2013
    ..Agents that site- specifically reduce metabolic ROS production and subsequent HC loss will be identified as key pharmaceutical intermediates poised to reduce the ototoxicity experienced during clinical GM treatment. ..
  10. Ameliorating systemic gentamicin uptake by sensory hair cells
    PETER STEPHEN STEYGER; Fiscal Year: 2013
    ....
  11. Evaluating the efficiency and specificity of stop codon suppression therapy
    Michael T Howard; Fiscal Year: 2013
    ....
  12. p53 and aminoglycoside-induced hair cell death in the zebrafish lateral line
    Allison B Coffin; Fiscal Year: 2013
    ..Understanding how these sensory cells are damaged will help us design strategies to protect them, hopefully preventing hearing loss. ..
  13. Cochlear trafficking and hair cell uptake of aminoglycosides
    PETER STEPHEN STEYGER; Fiscal Year: 2013
    ....
  14. Tuning aminoglycosides for treatment of genetic diseases
    Timor Baasov; Fiscal Year: 2013
    ..The proposed research aims to develop potent aminoglycosides derivatives with high potential for immediate therapeutic application for treatment of genetic diseases caused by nonsense mutations. ..
  15. Gentamicin for Improving Survival and Outcome after Subarachnoid Hemorrhage.
    Joshua B Bederson; Fiscal Year: 2013
    ..The proposed study is significant because it is expected to establish a therapeutic agent that could dramatically reduce early mortality and morbidity in a patient population for which currently no such therapy option exist. ..
  16. INNER EAR FLUID INTERACTIONS
    Alec N Salt; Fiscal Year: 2013
    ..This project seeks to develop an understanding of pharmacokinetics in the ear that will, in conjunction with computer models, allow drug treatment protocols to be scientifically based. ..
  17. Drug Discovery for the Prevention of Hearing Loss
    Julian A Simon; Fiscal Year: 2012
    ..Optimization of lead compounds and validation in a mammalian system will provide essential drug development information for future clinical trials in human patients. ..
  18. Drug Discovery for the Prevention of Hearing Loss
    Julian A Simon; Fiscal Year: 2013
    ..Optimization of lead compounds and validation in a mammalian system will provide essential drug development information for future clinical trials in human patients. ..
  19. Lung Injury and Shock Pathogenesis in Y. pestis Sepsis
    ANDREW LECHNER; Fiscal Year: 2006
    ..Aims 3 and 4 to be completed in Year 2 within BSL-3 labs.] ..
  20. Vestibular Prosthesis Tested in a Vestibulopathic Model
    Richard F Lewis; Fiscal Year: 2012
    ..Successful completion of this task would significantly improve the quality of life for a large number of people who suffer from the debilitating symptoms produced by disorders of the balance portion of the inner ear. ..
  21. Inhaled Aminoglycoside Formulafor Plague and Tularemia
    James Talton; Fiscal Year: 2005
    ..Specific Aim 3: Establish the efficacy of selected inhaled aminoglycoside formulation in post-exposure prophylaxis after a nasal challenge in mice. ..
  22. Mechanistic Studies of Deoxy Sugar Biosynthesis
    Hung wen Liu; Fiscal Year: 2013
    ..We believe this wor will continue to address standing questions in biological chemistry and open new avenues of discovery in secondary metabolism and pharmaceutical research. ..
  23. Can L-carnitine prevent drug-induced hearing loss?
    Gilda Kalinec; Fiscal Year: 2004
    ....
  24. Paper Spray Ionization Mass Spectrometry Device for Direct Analysis of Biofluid S
    Zheng Ouyang; Fiscal Year: 2012
    ..It has strong relevance to general public health by providing a tool for fast, easy, highly sensitive and selective chemical monitoring for clinical diagnosis or personal health care. ..
  25. Paper Spray Ionization Mass Spectrometry Device for Direct Analysis of Biofluid S
    Zheng Ouyang; Fiscal Year: 2011
    ..It has strong relevance to general public health by providing a tool for fast, easy, highly sensitive and selective chemical monitoring for clinical diagnosis or personal health care. ..
  26. Functional similarities in renal and cochlear epithelia
    PETER STEYGER; Fiscal Year: 2004
    ....
  27. Transduction of the Mouse Auditory System with AAV
    DIANA LURIE; Fiscal Year: 2003
    ..The focus of these future studies will be on delivering specific genes to the auditory system that potentially play a role in both the functional recovery of the cochlea, as well as neuroprotection following cochlear damage. ..
  28. ROLE OF POLYAMINES IN POSTNATAL COCHLEAR DEVELOPMENT
    Charles Henley; Fiscal Year: 1993
    ....
  29. Preclinical Development of an Absorbable Antibacterial Bone Hemostatic Agent
    TIMOTHY FISHER; Fiscal Year: 2009
    ..g., Avitene). Thus, once developed, the Ostene+ Gentamicin combination would be not expected to meet any major barrier to acceptance. ..
  30. MECHANISM FOR CHARGED-RELATED NEPHROTOXICITY
    Darryl Peterson; Fiscal Year: 1993
    ..The effects of cationized albumin and gentamicin on membrane shuttling and Na/H antiporter activity will be measured in microperfused proximal nephron segments and isolated renal membranes...
  31. ELECTRON TRANSPORT VARIANTS IN STAPHYLOCOCCAL DISEASE
    Richard Proctor; Fiscal Year: 2001
    ..For example, with overwhelming sepsis, rapidly shutting off virulence factors is desirable; whereas preventing ETV formation may allow for more effective therapy of chronic infections. ..
  32. Campylobacter jejuni and Reactive Nitrogen Species
    Nicole Iovine; Fiscal Year: 2007
    ..jejuni. The co-sponsorship of this award provides a rich environment in which the trainee will gain the technical and professional development needed to become an independent investigator. ..
  33. HAIR CELL REGENERATION IN THE VESTIBULAR OTOLITH ORGANS
    Richard Baird; Fiscal Year: 2001
    ....
  34. Mechanisms and Key Molecular Target of Gentamacin Toxicity
    Bruce A Molitoris; Fiscal Year: 2013
    ..Finally, we will use siRNA to directly probe target molecules as we have previously demonstrated with p53 in proximal tubule cells using siRNA in rats. ..
  35. E COLI TRANSLOCATION ACROSS INTESTINAL EPITHELIUM
    Michelle Pietzak; Fiscal Year: 2003
    ..abstract_text> ..
  36. Vestibular Hair Cell Regeneration
    LARRY HOFFMAN; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  37. OXY-RADICALS IN GENTAMICIN AND OTHER TOXIC NEPHROPATHIES
    Patrick Walker; Fiscal Year: 1992
    ..g. other aminoglycoside-induced (Tobramycin, etc.), endotoxin-induced, glycerol-induced, and uranyl nitrate-induced ARF...
  38. OXIDATIVE NEUTROPHIL MICROBICIDAL MECHANISMS
    Henry Rosen; Fiscal Year: 2000
    ..The anticipated benefit of the project is an improved understanding of PMN- mediated host defense against bacterial infection. ..
  39. Electrical Stimulation to Restore Vestibular Function
    CHARLES DELLA SANTINA; Fiscal Year: 2007
    ..We will test whether stimulation of canals in a single labyrinth can be combined to drive eye movements that cover the normal physiologic range. [unreadable] [unreadable]..
  40. A new absorbable antimicrobial bone graft substitute
    David Martin; Fiscal Year: 2005
    ..Proposed experiments will employ bone matrix studies to demonstrate the dual utility of this polymeric composition. ..
  41. IRIS PIGMENTATION, MELANINS AND OCULAR DRUG EFFECTS
    POPAT PATIL; Fiscal Year: 1980
    ..Details of kinetics of binding of selected aminoglycoside on the isolated melanins and melanin granules will be studied to understand the relevancy of binding to the toxicity. ..
  42. Role of P53 in Aminoglycoside Ototoxicity
    Mei Zhang; Fiscal Year: 2009
    ..The outcome of the study will have clinical application toward developing new therapies to protect against drug-induced ototoxicity and will contribute to the understanding of the molecular mechanisms of drug-induced ototoxicity. ..
  43. Translational Bypass in Patients with Hemophilia
    Steve Sommer; Fiscal Year: 2003
    ..Nonsense suppressors also may be beneficial in the treatment of cancers that result from nonsense mutation in tumor suppressor genes. ..
  44. OTOTOXIC MECHANISMS OF GENTAMICIN ON SENSORY HAIR CELLS
    Hong Yan; Fiscal Year: 1993
    ..Lithium blockage" hypothesis could be proved if no ototoxic damage is detected at striolar hair cells...
  45. Differences in neomycin and gentamicin toxicity in the zebrafish lateral line
    ALLISON COFFIN; Fiscal Year: 2009
    ..This research looks at specific molecules underlying hair cell death in response to antibiotics and will examine ways to prevent this death, potentially providing new therapeutic targets for prevention of hearing loss. ..
  46. Molecular studies of hair cell death
    Alan Cheng; Fiscal Year: 2001
    ..Knowledge gained from these studies will provide new insights on key mediators in hair cell death and contribute to the development of better otoprotective therapies. ..
  47. ULTRASONIC/ANTIBIOTIC THERAPY--INFECTED IMPLANT IN VIVO
    WILLIAM PITT; Fiscal Year: 2000
    ..If this is the case, this therapy has potential to relieve the pain and eliminate the need for replacement surgery for thousands of people who have implant infections. ..
  48. Gentamicin Trial in Duchenne and Limb Girdle Dystrophies
    Jerry Mendell; Fiscal Year: 2004
    ..Gentamicin will also be used to treat limb girdle muscular dystrophy subjects with stop codon mutations. If the serum CK is lowered, the potential for long-term treatment will be established for these patients. ..
  49. MECHANISMS OF ANTIBIOTIC RESISTANCE IN MICROORGANISMS
    Julian Davies; Fiscal Year: 1980
    ..d) Studies of the plasmid and enzyme epidemiology of hospital outbreaks of resistant organisms will be continued. ..
  50. Mechanism of nonsense mutation suppression therapy
    Allan Jacobson; Fiscal Year: 2007
    ....
  51. Gfil in sensory neuron and hair cell development
    DEEANN WALLIS SCHULTZ; Fiscal Year: 2003
    ..This is clinically significant as a gene therapy based approach to treat inner ear hair cell loss or damage has immense applications for the hearing and balance impaired. ..
  52. Traversal mechanism of epithelial cells by P. aeruginosa
    Irania Alarcon; Fiscal Year: 2007
    ..Extracellular travel will be studied using time-lapse video microscopy and dm. ..
  53. Inhibition of Gentamicin-Induced Cochlear Hair Cell Death
    Christina Kaiser; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  54. Vestibular Recovery after Intratympanic Gentamicin
    John Carey; Fiscal Year: 2004
    ..Furthermore, the mechanisms of vestibular recovery may help us understand the potential for the inner ear to recover from a variety of injuries. ..
  55. VESTIBULAR EFFECTS OF INTRATYMPANIC GENTAMICIN
    John Carey; Fiscal Year: 2005
    ..Johns Hopkins is uniquely suited to this training because it has a core group devoted to vestibular research, and the mentor's laboratory has successfully used all of the techniques required. ..
  56. Evalution of Vestibular Function in Meniere's Disease
    John Carey; Fiscal Year: 2009
    ..Comparisons of angular and translational VOR deficits after intratympanic gentamicin should demonstrate whether or not the utricle is less susceptible than the semicircular canals to intratympanic gentamicin. ..
  57. Beta-defensins and pulmonary host defense
    Timothy Starner; Fiscal Year: 2006
    ..This environment will maximize the potential for the principal investigator to establish himself in a basic science career as an academic independent investigator. ..
  58. MUCOSAL DEFENSE MECHANISMS IN SUBSTANCE ABUSE
    David R Brown; Fiscal Year: 2010
    ....
  59. Mechanism of Opiate Induced Audiovestibular Dysfunction
    Gail Ishiyama; Fiscal Year: 2006
    ....
  60. Galvanic Effects on the Human Vestibuloocular Reflex
    Americo Migliaccio; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  61. Technology and Endothelial Biology of Kidney Injury Molecule-1
    Vishal Vaidya; Fiscal Year: 2007
    ..unreadable] [unreadable]..