L Amaral

Summary

Affiliation: Instituto de Higiene e Medicina Tropical
Country: Portugal

Publications

  1. ncbi request reprint Enhanced killing of intracellular multidrug-resistant Mycobacterium tuberculosis by compounds that affect the activity of efflux pumps
    Leonard Amaral
    Unidade de Micobacterias, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, Lisboa, Portugal
    J Antimicrob Chemother 59:1237-46. 2007
  2. ncbi request reprint Intracellular activity of clinical concentrations of phenothiazines including thioridiazine against phagocytosed Staphylococcus aureus
    Diane Ordway
    Unit of Mycobacteriology, Department of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 019 Lisboa, Portugal
    Int J Antimicrob Agents 20:34-43. 2002
  3. ncbi request reprint An instrument-free method for the demonstration of efflux pump activity of bacteria
    Marta Martins
    Unidade de Micobacterias, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    In Vivo 20:657-64. 2006
  4. ncbi request reprint Inhibitors of Ca2+ and K+ transport enhance intracellular killing of M. tuberculosis by non-killing macrophages
    Marta Martins
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, 1349 008 Lisboa, Portugal
    In Vivo 22:69-75. 2008
  5. ncbi request reprint Identification of efflux pump-mediated multidrug-resistant bacteria by the ethidium bromide-agar cartwheel method
    Marta Martins
    Unit of Mycobacteriology and UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT UNL, Rua da Junqueira, 100, 1349 008 Lisbon, Portugal
    In Vivo 25:171-8. 2011
  6. ncbi request reprint The Mechanism by which the Phenothiazine Thioridazine Contributes to Cure Problematic Drug-Resistant Forms of Pulmonary Tuberculosis: Recent Patents for "New Use"
    Leonard Amaral
    Travel Medicine, Centro de Malária Doenças Tropicais, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 100, 1349 008 Lisbon, Portugal
    Recent Pat Antiinfect Drug Discov 8:206-12. 2013
  7. pmc Antibiotic stress, genetic response and altered permeability of E. coli
    Miguel Viveiros
    Unit of Mycobacteriology, Unidade de Parasitologia e Microbiologia Médicas UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal
    PLoS ONE 2:e365. 2007
  8. pmc pH Modulation of efflux pump activity of multi-drug resistant Escherichia coli: protection during its passage and eventual colonization of the colon
    Ana Martins
    Unit of Mycobacteriology, Universidade Nova de Lisboa IHMT UNL, Lisboa, Portugal
    PLoS ONE 4:e6656. 2009
  9. ncbi request reprint Mechanisms by which thioridazine in combination with antibiotics cures extensively drug-resistant infections of pulmonary tuberculosis
    Leonard Amaral
    Travel Medicine of the Center de Malaria e Doencas Tropicais, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisbon, Portugal
    In Vivo 28:267-71. 2014
  10. ncbi request reprint The in vitro activity of products formed from exposure of chlorpromazine to a 266 nm laser beam against species of mycobacteria of human interest
    Ana Maria Armada
    Center from Malaria and Other Tropical Diseases CMDT, Institute of Hygiene and Tropical Medicine IHMT, New University of Lisbon, Lisbon, Portugal
    In Vivo 27:605-10. 2013

Collaborators

Detail Information

Publications85

  1. ncbi request reprint Enhanced killing of intracellular multidrug-resistant Mycobacterium tuberculosis by compounds that affect the activity of efflux pumps
    Leonard Amaral
    Unidade de Micobacterias, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, Lisboa, Portugal
    J Antimicrob Chemother 59:1237-46. 2007
    ....
  2. ncbi request reprint Intracellular activity of clinical concentrations of phenothiazines including thioridiazine against phagocytosed Staphylococcus aureus
    Diane Ordway
    Unit of Mycobacteriology, Department of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 019 Lisboa, Portugal
    Int J Antimicrob Agents 20:34-43. 2002
    ..These results suggest that TZ induces intracellular bactericidal activities independent of the capacity to generate Type 1 responses against S. aureus...
  3. ncbi request reprint An instrument-free method for the demonstration of efflux pump activity of bacteria
    Marta Martins
    Unidade de Micobacterias, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    In Vivo 20:657-64. 2006
    ....
  4. ncbi request reprint Inhibitors of Ca2+ and K+ transport enhance intracellular killing of M. tuberculosis by non-killing macrophages
    Marta Martins
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, 1349 008 Lisboa, Portugal
    In Vivo 22:69-75. 2008
    ..The aim of this study was to evaluate the effect of inhibitors such as ouabain, reserpine and verapamil in the killing activity of macrophages infected with Mycobacterium tuberculosis...
  5. ncbi request reprint Identification of efflux pump-mediated multidrug-resistant bacteria by the ethidium bromide-agar cartwheel method
    Marta Martins
    Unit of Mycobacteriology and UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT UNL, Rua da Junqueira, 100, 1349 008 Lisbon, Portugal
    In Vivo 25:171-8. 2011
    ..The agar-based method, previously reported, has been modified to evaluate as many as twelve bacterial strains and has been termed the ethidium bromide-agar cartwheel method...
  6. ncbi request reprint The Mechanism by which the Phenothiazine Thioridazine Contributes to Cure Problematic Drug-Resistant Forms of Pulmonary Tuberculosis: Recent Patents for "New Use"
    Leonard Amaral
    Travel Medicine, Centro de Malária Doenças Tropicais, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 100, 1349 008 Lisbon, Portugal
    Recent Pat Antiinfect Drug Discov 8:206-12. 2013
    ..Given that economic motivation can stimulate the use of this drug as an antitubercular agent, future prospects are also discussed. ..
  7. pmc Antibiotic stress, genetic response and altered permeability of E. coli
    Miguel Viveiros
    Unit of Mycobacteriology, Unidade de Parasitologia e Microbiologia Médicas UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal
    PLoS ONE 2:e365. 2007
    ..The number and activity of efflux pumps and outer membrane proteins that constitute porins play major roles in the definition of intrinsic resistance in Gram-negative bacteria that is altered under antibiotic exposure...
  8. pmc pH Modulation of efflux pump activity of multi-drug resistant Escherichia coli: protection during its passage and eventual colonization of the colon
    Ana Martins
    Unit of Mycobacteriology, Universidade Nova de Lisboa IHMT UNL, Lisboa, Portugal
    PLoS ONE 4:e6656. 2009
    ..The herein described study examines the effect of pH on the extrusion of ethidium bromide (EB)...
  9. ncbi request reprint Mechanisms by which thioridazine in combination with antibiotics cures extensively drug-resistant infections of pulmonary tuberculosis
    Leonard Amaral
    Travel Medicine of the Center de Malaria e Doencas Tropicais, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisbon, Portugal
    In Vivo 28:267-71. 2014
    ..This mini-review discusses the mechanisms that render TZ an effective adjuvant to antibiotics to which the initial infective agent Mtb was resistant...
  10. ncbi request reprint The in vitro activity of products formed from exposure of chlorpromazine to a 266 nm laser beam against species of mycobacteria of human interest
    Ana Maria Armada
    Center from Malaria and Other Tropical Diseases CMDT, Institute of Hygiene and Tropical Medicine IHMT, New University of Lisbon, Lisbon, Portugal
    In Vivo 27:605-10. 2013
    ..Of significant note is that the irradiation products of CPZ had lower in vitro cytotoxicity against human cells, suggesting that this approach may be useful for the development of compounds more bioactive than the parental species...
  11. doi request reprint Why and how thioridazine in combination with antibiotics to which the infective strain is resistant will cure totally drug-resistant tuberculosis
    Leonard Amaral
    Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 100, 1349 008 Lisbon, Portugal
    Expert Rev Anti Infect Ther 10:869-73. 2012
    ..tuberculosis normally resides during infection, and coupled to the inhibition of efflux pumps which contribute to the antibiotic-resistant status, effective therapy of any antibiotic-resistant TB infection is possible...
  12. ncbi request reprint Inhibitors of bacterial efflux pumps that also inhibit efflux pumps of cancer cells
    Leonard Amaral
    Group of Mycobacteriology, Unit of Medical Microbiologiy, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisbon, Portugal
    Anticancer Res 32:2947-57. 2012
    ..This review aims to identify such agents...
  13. doi request reprint Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections
    Leonard Amaral
    Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 100, 1049 008 Lisbon, Portugal
    Int J Antimicrob Agents 39:376-80. 2012
    ..The combination of these effects of TDZ probably contributes to the successful recent cures of XDR-TB cases when the phenothiazine TDZ is used in combination with antibiotics to which the patient with XDR-TB was initially unresponsive...
  14. ncbi request reprint Rapid, laser-induced conversion of 20-hydroxyecdysone and its diacetonide -- experimental set-up of a system for photochemical transformation of bioactive substances
    A Hunyadi
    Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
    Anticancer Res 32:1291-7. 2012
    ....
  15. ncbi request reprint Potential therapy of multidrug-resistant and extremely drug-resistant tuberculosis with thioridazine
    Leonard Amaral
    Group of Mycobacteriology, Unit of Medical Microbiology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisbon, Portugal
    In Vivo 26:231-6. 2012
    ..A recommended protocol is presented...
  16. ncbi request reprint Activity of fourteen new hydantoin compounds on the human ABCB1 efflux pump
    Ana Martins
    Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
    In Vivo 26:293-7. 2012
    ..The overexpression of an ABC transporter, the ABCB1, is often associated with MDR in cancer. Previously it was observed that hydantoin compounds can modulate the activity of the ABCB1 pump...
  17. ncbi request reprint Screening for efflux pump systems of bacteria by the new acridine orange agar method
    Ana Martins
    Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
    In Vivo 26:203-6. 2012
    ..Development of a non-toxic, fluorescent-based, agar system for the screening of overexpressed bacterial efflux pump systems with common, inexpensive UV accessories...
  18. ncbi request reprint The activity of 16 new hydantoin compounds on the intrinsic and overexpressed efflux pump system of Staphylococcus aureus
    Anna Dymek
    Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Krakow, Poland
    In Vivo 26:223-9. 2012
    ..To evaluate a new series of 16 hydantoin derivatives for activity against the intrinsic and overexpressed efflux pumps of the ATTC 25923 Staphylococcus aureus and the clinical Staphylococcus aureus HPV-107 strain, respectively...
  19. pmc Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus
    Sofia Santos Costa
    Grupo de Micobacterias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT, UNL, Rua da Junqueira 100, Lisbon, Portugal
    BMC Microbiol 11:241. 2011
    ..aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones...
  20. pmc Ethidium bromide transport across Mycobacterium smegmatis cell-wall: correlation with antibiotic resistance
    Liliana Rodrigues
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 100, 1349 008 Lisboa, Portugal
    BMC Microbiol 11:35. 2011
    ..This information was then correlated with minimum inhibitory concentrations (MICs) of several antibiotics in the presence or absence of the efflux inhibitors chlorpromazine, thioridazine and verapamil...
  21. ncbi request reprint Antimicrobial activity of phenothiazines
    Leonard Amaral
    Unit of Mycobacteriology UPMM Instituto de Higiene e Medicina Tropical Universidade de Lisboa, 1394 008 Lisbon, Portugal
    In Vivo 18:725-31. 2004
    ....
  22. ncbi request reprint Review. Comparison of multidrug resistant efflux pumps of cancer and bacterial cells with respect to the same inhibitory agents
    Leonard Amaral
    Unit of Mycobacteriology, UPMM, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, 1349 088 Lisboa, Portugal
    In Vivo 21:237-44. 2007
    ....
  23. ncbi request reprint Promising therapy of XDR-TB/MDR-TB with thioridazine an inhibitor of bacterial efflux pumps
    L Amaral
    Unit of Mycobacteriology, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT UNL, Lisboa, Portugal
    Curr Drug Targets 9:816-9. 2008
    ..When the prognosis is poor, available therapy predictably ineffective and death is inevitable, compassionate therapy with TZ should be contemplated. The risks are small and the rewards great...
  24. ncbi request reprint Activity of phenothiazines against antibiotic-resistant Mycobacterium tuberculosis: a review supporting further studies that may elucidate the potential use of thioridazine as anti-tuberculosis therapy
    L Amaral
    Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisbon, Portugal
    J Antimicrob Chemother 47:505-11. 2001
    ..Nevertheless, further in vitro and in vivo studies are essential before thioridazine may be recommended for the management of select cases of pulmonary tuberculosis...
  25. ncbi request reprint "Non-Antibiotics": alternative therapy for the management of MDRTB and MRSA in economically disadvantaged countries
    Leonard Amaral
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, UPMM, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008, Lisboa, Portugal
    Curr Drug Targets 7:887-91. 2006
    ..For these highly selective and controlled situations, the use of thioridazine in the manner employed for the therapy of psychosis is recommended (compassionate therapy)...
  26. ncbi request reprint Therapy Of XDR TB with thioridazine a drug beyond patent protection but eligible for patent "as new use"
    Leonard Amaral
    Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa Lisbon, Portugal
    Recent Pat Antiinfect Drug Discov 5:109-14. 2010
    ..Although thioridazine is beyond patent protection, its use for the therapy of XDR TB is new and therefore, a patent may be sought for "use as an anti-XDR TB agent"...
  27. doi request reprint Thioridazine cures extensively drug-resistant tuberculosis (XDR-TB) and the need for global trials is now!
    Leonard Amaral
    Unit of Mycobacteriology UPMM, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisbon, Portugal
    Int J Antimicrob Agents 35:524-6. 2010
    ..Because XDR-TB is essentially a terminal disease in many areas of the world and no new effective agents have yet to yield successful clinical trials, global clinical trials for the therapy of XDR-TB are urgently required...
  28. ncbi request reprint Phenothiazines, bacterial efflux pumps and targeting the macrophage for enhanced killing of intracellular XDRTB
    Leonard Amaral
    Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 96, 1349 008 Lisbon, Portugal
    In Vivo 24:409-24. 2010
    ..The mechanism by which this phenothiazine produces the desired effects within the infected macrophage is also discussed...
  29. ncbi request reprint Phenothiazines as anti-multi-drug resistant tubercular agents
    L Amaral
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    Infect Disord Drug Targets 7:257-65. 2007
    ..In vitro studies if not complemented by ex vivo studies will for the most part be dead-ended since few agents that have activity in vitro have any activity against phagocytosed M. tuberculosis...
  30. ncbi request reprint Thioridazine induces apoptosis of multidrug-resistant mouse lymphoma cells transfected with the human ABCB1 and inhibits the expression of P-glycoprotein
    Gabriella Spengler
    Institute of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary
    Anticancer Res 31:4201-5. 2011
    ....
  31. ncbi request reprint Phenothiazines: potential alternatives for the management of antibiotic resistant infections of tuberculosis and malaria in developing countries
    L Amaral
    Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisboa, Portugal
    Trop Med Int Health 6:1016-22. 2001
    ....
  32. doi request reprint Ethidium bromide efflux by Salmonella: modulation by metabolic energy, pH, ions and phenothiazines
    Leonard Amaral
    Grupo de Micobacterias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 100, 1349 008 Lisboa, Portugal
    Int J Antimicrob Agents 38:140-5. 2011
    ..Similarly, thioridazine, an inhibitor of metabolic enzymes, inhibits efflux of EtBr only at pH 8 and the degree of inhibition is lessened by the presence of metabolic energy...
  33. ncbi request reprint Effective therapy with the neuroleptic thioridazine as an adjunct to second line of defence drugs, and the potential that thioridazine offers for new patents that cover a variety of "new uses"
    Leonard Amaral
    Grupo de Micobacterias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Portugal
    Recent Pat Antiinfect Drug Discov 6:84-7. 2011
    ....
  34. ncbi request reprint Phenothiazines: potential management of Creutzfeldt-Jacob disease and its variants
    L Amaral
    Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 96, 1349 008, Lisbon, Portugal
    Int J Antimicrob Agents 18:411-7. 2001
    ..In this review we present direct and circumstantial evidence in support of a model describing the manner by which the intracellular antimicrobial activity of phenothiazines might cause the destruction of intracellular prions...
  35. doi request reprint Antibacterial properties of compounds isolated from Carpobrotus edulis
    A Martins
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisbon, Portugal
    Int J Antimicrob Agents 37:438-44. 2011
    ..Oleanolic acid presented high antibacterial activity against a large number of bacterial strains. The triterpene uvaol was the most active compound for modulation of efflux activity by MDR Gram-positive strains...
  36. doi request reprint Physiological characterisation of the efflux pump system of antibiotic-susceptible and multidrug-resistant Enterobacter aerogenes
    A Martins
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    Int J Antimicrob Agents 36:313-8. 2010
    ..e. proton-motive force-dependent and ABC transporter types, respectively...
  37. ncbi request reprint Enhancement of antibiotic activity against poly-drug resistant Mycobacterium tuberculosis by phenothiazines
    M Viveiros
    Mycobacteriology Unit, The Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 96, 1349-008, Lisbon, Portugal
    Int J Antimicrob Agents 17:225-8. 2001
    ..tuberculosis resistant to two or more antibiotics (poly-drug resistant MTB). The phenothiazines had no effect on the activity of isoniazid against poly-drug resistant MTB...
  38. ncbi request reprint New methods for the identification of efflux mediated MDR bacteria, genetic assessment of regulators and efflux pump constituents, characterization of efflux systems and screening for inhibitors of efflux pumps
    M Viveiros
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT UNL, Lisboa, Portugal
    Curr Drug Targets 9:760-78. 2008
    ..Because each method provides good reproducibility, they lend themselves for inter-laboratory use...
  39. doi request reprint An AcrAB-mediated multidrug-resistant phenotype is maintained following restoration of wild-type activities by efflux pump genes and their regulators
    A Martins
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal
    Int J Antimicrob Agents 34:602-4. 2009
    ....
  40. ncbi request reprint Targeting human macrophages for enhanced killing of intracellular XDR-TB and MDR-TB
    M Martins
    Unit of Mycobacteriology and Unidade de Parasitologia e Microbiologia Médicas UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT UNL, Lisboa, Portugal
    Int J Tuberc Lung Dis 13:569-73. 2009
    ....
  41. doi request reprint Identification of the plasmid-encoded qacA efflux pump gene in meticillin-resistant Staphylococcus aureus (MRSA) strain HPV107, a representative of the MRSA Iberian clone
    S S Costa
    Unidade de Micobacterias, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT, UNL, Rua da Junqueira 100, 1349 008 Lisbon, Portugal
    Int J Antimicrob Agents 36:557-61. 2010
    ..No association could be made with antibiotic resistance. This work emphasises the potential of QacA pump activity in the maintenance and dissemination of important MRSA strains in the hospital setting and, increasingly, in the community...
  42. ncbi request reprint Phenothiazines alter resistance of methicillin-resistant strains of Staphylococcus aureus (MRSA) to oxacillin in vitro
    Malthe M Kristiansen
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisbon, Portugal
    Int J Antimicrob Agents 22:250-3. 2003
    ..Reserpine, an inhibitor of antibiotic efflux pumps also reduced the resistance of MRSA strains to oxacillin suggesting the presence of an efflux pump that contributes to antibiotic resistance of MRSA strains...
  43. ncbi request reprint Thioridazine reduces resistance of methicillin-resistant staphylococcus aureus by inhibiting a reserpine-sensitive efflux pump
    Malthe M Kristiansen
    Unit of Mycobacteriology, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    In Vivo 20:361-6. 2006
    ..The phenothiazines have been shown, by others, to inhibit the efflux pumps of bacteria and the mechanism by which MRSA are rendered more susceptible to oxacillin in the presence of TZ is believed to be due to a similar efflux pump...
  44. ncbi request reprint Clinical concentrations of thioridazine enhance the killing of intracellular methicillin-resistant Staphylococcus aureus: an in vivo, ex vivo and electron microscopy study
    Marta Martins
    Unit of Mycobacteriology, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, 1349 019 Lisboa, Portugal
    In Vivo 18:787-94. 2004
    ....
  45. ncbi request reprint The effects of chlorpromazine on the outer cell wall of Salmonella typhimurium in ensuring resistance to the drug
    L Amaral
    Department of Clinical Microbiology, County of Sonderjylland, Sonderborg Sygehus, 6400, Sonderborg, Denmark
    Int J Antimicrob Agents 14:225-9. 2000
    ..The results also suggested that the CPZ binds to the 55 kDa protein and that such binding interfered with the recognition of the O antigen by antibody...
  46. doi request reprint Efflux-mediated response of Staphylococcus aureus exposed to ethidium bromide
    Isabel Couto
    Unidade de Micobacterias, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa UNL, Portugal
    J Antimicrob Chemother 62:504-13. 2008
    ..aureus adaptation to ethidium bromide...
  47. doi request reprint Molecular tools for rapid identification and novel effective therapy against MDRTB/XDRTB infections
    Miguel Viveiros
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT UNL, Rua da Junqueira, Lisbon, Portugal
    Expert Rev Anti Infect Ther 8:465-80. 2010
    ..tuberculosis isolated from the patient's sputum; and the mode of action by which phenothiazines have been shown to promote the killing of intracellular MDRTB/XDRTB by nonkilling macrophages...
  48. ncbi request reprint Mycobacterial efflux pumps and chemotherapeutic implications
    Miguel Viveiros
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisbon, Portugal
    Int J Antimicrob Agents 22:274-8. 2003
    ..During the course of tuberculosis chemotherapy many of these pumps might play a role in the survival of the mycobacterial populations. Compounds capable of inactivating these pumps could improve anti-tuberculous therapeutics...
  49. doi request reprint The role of efflux pumps in macrolide resistance in Mycobacterium avium complex
    Liliana Rodrigues
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT UNL, Lisboa, Portugal
    Int J Antimicrob Agents 34:529-33. 2009
    ..This study demonstrates that efflux pumps play an important role in MAC resistance to antibiotics...
  50. ncbi request reprint Inhibition of the Carpobrotus edulis methanol extract on the growth of phagocytosed multidrug-resistant Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus
    Marta Martins
    Unit of Mycobacteriology, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008, Lisboa, Portugal
    Fitoterapia 76:96-9. 2005
    ....
  51. doi request reprint Identification of nontuberculous mycobacteria in clinical samples using molecular methods: a 3-year study
    I Couto
    Unidade de Micobacterias, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT UNL, Lisbon, Portugal
    Clin Microbiol Infect 16:1161-4. 2010
    ..Introducing these methods for the rapid identification of NTM highlights the importance of NTM as potential pathogens and assisted the selection of adequate therapy...
  52. ncbi request reprint Constituents of Carpobrotus edulis inhibit P-glycoprotein of MDR1-transfected mouse lymphoma cells
    A Martins
    Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 96, 1349 008 Lisbon, Portugal
    Anticancer Res 30:829-35. 2010
    ..Uvaol was the most effective and promising compound in the reversal of multidrug resistance in MDR mouse lymphoma cell line...
  53. ncbi request reprint Carpobrotus edulis methanol extract inhibits the MDR efflux pumps, enhances killing of phagocytosed S. aureus and promotes immune modulation
    Diane Ordway
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    Phytother Res 17:512-9. 2003
    ..It is supposed that the resistance modifier and immunomodulatory effect of this plant extract can be exploited in the experimental chemotherapy of cancer and bacterial or viral infections...
  54. pmc Clinical concentrations of thioridazine kill intracellular multidrug-resistant Mycobacterium tuberculosis
    Diane Ordway
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, 1349 008 Lisbon, Portugal
    Antimicrob Agents Chemother 47:917-22. 2003
    ..tuberculosis isolates. Nevertheless, we must await the outcomes of clinical trials to determine whether TZ itself may be safely and effectively used as an antituberculosis agent...
  55. pmc Direct application of the INNO-LiPA Rif.TB line-probe assay for rapid identification of Mycobacterium tuberculosis complex strains and detection of rifampin resistance in 360 smear-positive respiratory specimens from an area of high incidence of multidrug
    Miguel Viveiros
    Unidade de Micobacterias do Instituto de Higiene e Medicina Tropical, Lisboa, Portugal
    J Clin Microbiol 43:4880-4. 2005
    ..7%; the sensitivity and specificity were 100.0% and 96.9%, respectively, for the detection of RIF resistance. This assay has the potential to provide rapid information that is essential for the effective management of MDR-TB...
  56. ncbi request reprint Prolonged exposure of methicillin-resistant Staphylococcus aureus (MRSA) COL strain to increasing concentrations of oxacillin results in a multidrug-resistant phenotype
    Ana Martins
    Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisbon, Portugal
    Int J Antimicrob Agents 29:302-5. 2007
    ..This is the first time that a multidrug-resistant phenotype has been experimentally produced as a consequence of exposure of the organism to an antibiotic to which it is initially highly resistant...
  57. ncbi request reprint In vitro and ex vivo activity of thioridazine derivatives against Mycobacterium tuberculosis
    Marta Martins
    Unidade de Micobacterias, UPMM, Instituto de Higiene e Medicina Tropical, Universidade de Lisboa, Rua da Junqueira 96, 1394 008 Lisbon, Portugal
    Int J Antimicrob Agents 29:338-40. 2007
    ..tuberculosis was evaluated with the aid of the BACTEC 460 system. Derivatives that presented significant activity were evaluated by ex vivo studies and were shown to enhance the killing of intracellular M. tuberculosis...
  58. doi request reprint Thioridazine and chlorpromazine inhibition of ethidium bromide efflux in Mycobacterium avium and Mycobacterium smegmatis
    Liliana Rodrigues
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    J Antimicrob Chemother 61:1076-82. 2008
    ..We have characterized the efflux pump activity of M. avium wild-type strain through an automated fluorometric method and correlated it with intrinsic resistance to antibiotics...
  59. ncbi request reprint The in vitro activity of phenothiazines against Mycobacterium avium: potential of thioridazine for therapy of the co-infected AIDS patient
    Miguel Viveiros
    Unit of Mycobacteriology, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 019 Lisboa, Portugal
    In Vivo 19:733-6. 2005
    ..10 to > 50 mg/L, as was previously shown for M. tuberculosis, thioridazine was the most active of the group against M. avium...
  60. ncbi request reprint The curative activity of thioridazine on mice infected with Mycobacterium tuberculosis
    Marta Martins
    Unit of Mycobacteriology, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    In Vivo 21:771-5. 2007
    ..The aim of the study was to evaluate the effectiveness of thioridazine (TZ) at different dose levels on mice that had been infected intraperitoneally (i.p.) with a high dose of the Mycobacterium tuberculosis ATCC H37Rv strain...
  61. ncbi request reprint Since phenothiazines alter antibiotic susceptibility of microorganisms by inhibiting efflux pumps, are these agents useful for evaluating similar pumps in phenothiazine-sensitive parasites?
    Maria Amelia Gracio
    Unidade de Helmintologia e Parasitologia Medica, Unidade de Entemologia, Universidade Nova de Lisboa, Rua da Junqueira 96, Lisbon 1349 008, Portugal
    Int J Antimicrob Agents 22:347-51. 2003
    ..Because these agents are inexpensive and many are no longer protected by patent, they may be exploited as anti-parasitic agents in the poorer areas of the world...
  62. doi request reprint SILA 421, an inhibitor of efflux pumps of cancer cells, enhances the killing of intracellular extensively drug-resistant tuberculosis (XDR-TB)
    Marta Martins
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT UNL, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    Int J Antimicrob Agents 33:479-82. 2009
    ..Because SILA 421 revealed good in vitro and ex vivo activities and is devoid of any cytotoxic activity, it is a potential candidate as an anti-MDR/XDR-TB drug...
  63. doi request reprint The TB laboratory of the future: macrophage-based selection of XDR-TB therapeutics
    Marta Martins
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira, 96, 1349 008 Lisboa, Portugal
    Future Microbiol 3:135-44. 2008
    ..This system is reviewed in its entirety and its potential and feasibility are supported by hard experimental demonstrations...
  64. ncbi request reprint Chlorpromazine has intracellular killing activity against phagocytosed Staphylococcus aureus at clinical concentrations
    Diane Ordway
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 019 Lisbon, Portugal
    J Infect Chemother 8:227-31. 2002
    ..Therefore, CPZ may have a role in the management of intracellular staphylococcal infections that normally require the use of antibiotics whose potential toxicity exceeds that associated with short-term management with CPZ...
  65. pmc Isoniazid-induced transient high-level resistance in Mycobacterium tuberculosis
    Miguel Viveiros
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, P 1349 008 Lisbon, Portugal
    Antimicrob Agents Chemother 46:2804-10. 2002
    ..These results collectively suggest that high-level resistance to INH can be induced in INH-susceptible M. tuberculosis strains by the induction of a reserpine-sensitive efflux mechanism...
  66. ncbi request reprint Increased Interleukin-4 production by CD8 and gammadelta T cells in health-care workers is associated with the subsequent development of active tuberculosis
    Diane J Ordway
    Centro de Malaria e Outras Doencas Tropicais, Unit of Mycobacteriology Instituto de Higiene e Medicina Tropical, Universidade de Lisboa, Hospital Egas Moniz, Lisbon, Portugal
    J Infect Dis 190:756-66. 2004
    ..HCWs who remained healthy showed increased median percentages of CD8+IFN- gamma+ (25.0%) and gammadelta +IFN- gamma+ (8.0%) and lower percentages of CD8+IL-4+ (0.05%) and gammadelta +IL-4+ (0.03%) T cells...
  67. ncbi request reprint Demonstration of the activity of P-glycoprotein by a semi-automated fluorometric method
    Gabriella Spengler
    Unit of Mycobacteriology, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa IHMT UNL, 1349 008 Lisboa, Portugal
    Anticancer Res 29:2173-7. 2009
    ....
  68. ncbi request reprint Biological activity of twenty-three hydantoin derivatives on intrinsic efflux pump system of Salmonella enterica serovar Enteritidis NCTC 13349
    Lisa Machado
    Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisbon, Portugal
    In Vivo 25:769-72. 2011
    ....
  69. ncbi request reprint Evaluation of forty new phenothiazine derivatives for activity against intrinsic efflux pump systems of reference Escherichia coli, Salmonella Enteritidis, Enterococcus faecalis and Staphylococcus aureus strains
    Daniella Takács
    Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    In Vivo 25:719-24. 2011
    ..Because phenothiazines inhibit efflux pumps of bacteria, forty new phenothiazine derivatives were tested for their inhibition of the efflux pump systems of Gram-positive and Gram-negative pathogenic bacteria...
  70. ncbi request reprint Competition between substrates of the efflux pump system of Salmonella enteritidis
    Pedro Cerca
    Grupo de Micobacterias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal
    In Vivo 25:597-602. 2011
    ..To determine whether tetracycline competes with ethidium bromide (EB), used as substrate of efflux pumps, for extrusion by the efflux pump system of Salmonella enteritidis NCTC 13349 reference strain...
  71. ncbi request reprint Biological activity of hydantoin derivatives on P-glycoprotein (ABCB1) of mouse lymphoma cells
    Gabriella Spengler
    Unit of Mycobacteriology and 2Unidade de Parasitologia e Microbiologia Medicas, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa Lisboa, Portugal
    Anticancer Res 30:4867-71. 2010
    ..Hydantoin derivatives possess a variety of biochemical and pharmacological properties. Although hydantoin compounds are studied extensively, there are not many studies that investigate their anticancer properties...
  72. ncbi request reprint Gamma delta T cell responses associated with the development of tuberculosis in health care workers
    Diane J Ordway
    Centro de Malaria e Outras Doencas Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1394 008 Lisbon, Portugal
    FEMS Immunol Med Microbiol 43:339-50. 2005
    ..Our results suggest that HCWs who developed TB show an early compensatory mechanism involving an increase in lytic responses of gammadelta TCR+ cells which did not prevent TB...
  73. ncbi request reprint Evaluation of cucurbitane-type triterpenoids from Momordica balsamina on P-glycoprotein (ABCB1) by flow cytometry and real-time fluorometry
    Gabriella Spengler
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    Anticancer Res 29:3989-93. 2009
    ..A compound that can inhibit the activity of these transporters may find use as an adjunct to chemotherapy that had been rendered ineffective...
  74. ncbi request reprint Characterization of intrinsic efflux activity of Enterococcus faecalis ATCC29212 by a semi-automated ethidium bromide method
    Gabriella Spengler
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Faculdade de Ciêncas e Tecnologia, Universidade Nova de Lisboa, Lisboa, Portugal
    In Vivo 23:81-7. 2009
    ..These results are relevant to infections produced by E. faecalis and subsequent antibiotic therapy with antibiotics to which the organism is known to be intrinsically resistant...
  75. doi request reprint Demonstration of intrinsic efflux activity of Escherichia coli K-12 AG100 by an automated ethidium bromide method
    Miguel Viveiros
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, Lisbon, Portugal
    Int J Antimicrob Agents 31:458-62. 2008
    ..The method can be used for screening compound libraries for efflux inhibiting capacity...
  76. pmc Inducement and reversal of tetracycline resistance in Escherichia coli K-12 and expression of proton gradient-dependent multidrug efflux pump genes
    Miguel Viveiros
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua Junqueira 96, 1349 008 Lisbon, Portugal
    Antimicrob Agents Chemother 49:3578-82. 2005
    ..All transporter genes were overexpressed after induced resistance with acrF being 80-fold more expressed in the DeltaacrAB tetracycline-induced strain...
  77. doi request reprint Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant Gram-negative infections: mechanisms for their direct and indirect activities
    Marta Martins
    Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisboa, Portugal
    Int J Antimicrob Agents 31:198-208. 2008
    ..Although not all of the EPIs may serve a helper role owing to their toxicity, they may nevertheless serve as lead compounds...
  78. ncbi request reprint Antibacterial activity of ergosterol peroxide against Mycobacterium tuberculosis: dependence upon system and medium employed
    Noelia Duarte
    Centro de Estudos de Ciências Farmacêuticas, Faculty of Pharmacy, University of Lisbon, Av das Forcas Armadas, 1600 083 Lisboa, Portugal
    Phytother Res 21:601-4. 2007
    ..Ergosterol peroxide is also shown by the current study to be devoid of any activity against an antibiotic sensitive ATCC strain of Staphylococcus aureus...
  79. ncbi request reprint The mechanism of plasmid curing in bacteria
    Gabriella Spengler
    Institute of Medical Microbiology and Immunobiology, Albert Szent Gyorgyi Medical Centre, University of Szeged, Szeged, Hungary
    Curr Drug Targets 7:823-41. 2006
    ..Plasmid elimination in vitro provides a method of isolating plasmid free bacteria for biotechnology without any risk of inducing mutations...
  80. ncbi request reprint Elimination of plasmids by SILA compounds that inhibit efflux pumps of bacteria and cancer cells
    Zsuzsanna Schelz
    Department of Medical Microbiology, University of Szeged, 6720 Szeged, Hungary
    In Vivo 21:635-9. 2007
    ..In addition, because plasmid-mediated resistance is often found in tetracycline-treated cattle, SILA compound 421 may have potential as an adjunct during the time that the cattle are maintained on tetracycline prior to slaughter...
  81. ncbi request reprint Potential management of resistant microbial infections with a novel non-antibiotic: the anti-inflammatory drug diclofenac sodium
    Noton Kumar Dutta
    Institute of Laboratory Animal Resources, Laboratory Animal Medicine, College of Veterinary Medicine, 85 Dong, 733 Ho, Seoul National University, San 56 1, Sillim 9 Dong, Gwanakgu, Seoul, South Korea
    Int J Antimicrob Agents 30:242-9. 2007
    ..As was the case for the in vitro interaction, Dc in combination with streptomycin was even more effective. The non-antibiotic drug Dc has potential for the management of problematic antibiotic-resistant bacterial infections...
  82. ncbi request reprint Antiplasmid effect of promethazine in mixed bacterial cultures
    Annamaria Molnar
    Department of Medical Microbiology, University of Szeged, Dom ter 10, H 6720 Szeged, Hungary
    Int J Antimicrob Agents 22:217-22. 2003
    ..epidermidis. In our experiments the plasmid curing action of promethazine was more effective at elevated temperature than at lower temperatures...
  83. ncbi request reprint Control and regulation of permeability of MDR bacterial pathogens to antibiotics presented by COST Action BM0701
    Leonard Amaral
    Curr Drug Targets 9:718. 2008
  84. ncbi request reprint Synergistic interaction between proton pump inhibitors and resistance modifiers: promoting effects of antibiotics and plasmid curing
    Kristina Wolfart
    Department of Medical Microbiology, University of Szeged, 6720 Szeged, Dom ter 10, Hungary
    In Vivo 20:367-72. 2006
    ..coli and that it was this pump which, when inhibited by TF14, allowed more PMZ to reach its plasmid elimination target...
  85. ncbi request reprint The phenothiazinium chromophore and the evolution of antimalarial drugs
    Mark Wainwright
    Trop Med Int Health 10:501-11. 2005
    ..e. a multifactorial activity - underlines the utility of these compounds in antimalarial research either as single drugs or as adjuvants (partners in a drug combination), particularly in the face of resistant parasitic strains...