Adam Friedman | The George Washington University (original) (raw)

Papers by Adam Friedman

Virulence

Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, it... more Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine abscess model and compared with vancomycin. All treatment arms accelerated abscess clearance clinically, histologically, and by microbiological assays on both days 4 and 7 following infection. However, abscesses treated with NO-np via either route demonstrated a more substantial, statistically significant decrease in bacterial survival based on colony forming unit assays and histologically revealed less inflammatory cell infiltration and preserved muscular architecture. These data suggest that the NO...

Nanomedicine : nanotechnology, biology, and medicine, Jan 13, 2017

Systemic therapies are preferred for treating dermal dermatophytosis due to inadequate penetratio... more Systemic therapies are preferred for treating dermal dermatophytosis due to inadequate penetration of topical agents. However, systemic antifungals are associated with off-target effects and limited tissue penetration, and antimicrobial resistance is a growing concern. To address this, we investigated topical nitric oxide-releasing nanoparticles (NO-np), which have been used against superficial fungal infections and bacterial abscesses. In addition to enhanced penetration and permeation conferred by nanoparticles, nitric oxide, a broad-spectrum multi-mechanistic antimicrobial agent, offers decreased likelihood of resistance development. In the current study, NO-np inhibited Trichophyton rubrum in vitro, as well as in a murine model of dermal dermatophytosis. In mice, NO-np reduced fungal burden after three days, with complete clearance after seven. Furthermore, NO-np decreased tissue IL-2, 6, 10 and TNFα, indicating earlier attenuation of the host inflammatory response and decreased...

The Journal of investigative dermatology, Jan 14, 2015

Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 inflammasome was recently h... more Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. Nitric oxide (NO), a potent biological messenger, has documented broad-spectrum antimicrobial and immunomodulatory properties. To harness these characteristics to target acne, we utilized an established nanotechnology capable of generating/releasing nitric oxide over time (NO-np). P. acnes was found to be highly sensitive to all concentrations of NO-np tested, though human keratinocyte, monocyte, and embryonic zebra fish assays revealed no cytotoxicity. NO-np significantly suppressed IL-1β, TNF-α, IL-8 and IL-6 from human monocytes and IL-8 and IL-6 from human keratinocytes respectively. Importantly, silencing of NLRP3 expression by small interfering RNA did not limit NO-np inhibition of IL-1 β secretion from monocytes, and neither TNF-α, nor ...

Frontiers in microbiology, 2015

Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect a... more Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect areas rich in keratin such as hair, nails, and skin. Significantly, there are increasing rates of antimicrobial resistance among dermatophytes, especially for Trichophyton rubrum, the most frequent etiologic agent worldwide. Hence, investigators have been developing new therapeutic approaches, including photodynamic treatment. Photodynamic therapy (PDT) utilizes a photosensitive substance activated by a light source of a specific wavelength. The photoactivation induces cascades of photochemicals and photobiological events that cause irreversible changes in the exposed cells. Although photodynamic approaches are well established experimentally for the treatment of certain cutaneous infections, there is limited information about its mechanism of action for specific pathogens as well as the risks to healthy tissues. In this work, we have conducted a comprehensive review of the current knowle...

The Journal of chemical physics, Jan 21, 2007

Several theoretical models have been formulated to explain the growth of porous structures in ano... more Several theoretical models have been formulated to explain the growth of porous structures in anodized alumina. Using some basic assumptions, these models predict the size and shape of the pores in the anodic porous alumina as functions of pH and voltage. Additionally, they address issues of stability in the pore growth. In this work, we have carried out a systematic experimental investigation to study the stability phase diagram as a function of pH and applied voltage. We also obtain the dependence of pore dimensions on the pH, voltage, and acid type. Based on our results, and insight gained from recent chemical analysis of the porous alumina anodization process, we conclude that the models must include an appropriate weighting factor to account for the oxidation and dissolution mechanism during the pore formation.

Journal of Investigative Dermatology, 2015

Wound healing is a complex process driven largely by the migration of a variety of distinct cell ... more Wound healing is a complex process driven largely by the migration of a variety of distinct cell types from the wound margin into the wound zone. In this study, we identify the previously uncharacterized microtubule-severing enzyme, Fidgetin-like 2 (FL2), as a fundamental regulator of cell migration that can be targeted in vivo using nanoparticle-encapsulated small interfering RNA (siRNA) to promote wound closure and regeneration. In vitro, depletion of FL2 from mammalian tissue culture cells results in a more than twofold increase in the rate of cell movement, in part due to a significant increase in directional motility. Immunofluorescence analyses indicate that FL2 normally localizes to the cell edge, importantly to the leading edge of polarized cells, where it regulates the organization and dynamics of the microtubule cytoskeleton. To clinically translate these findings, we utilized a nanoparticle-based siRNA delivery platform to locally deplete FL2 in both murine full-thickness excisional and burn wounds. Topical application of FL2 siRNA nanoparticles to either wound type results in a significant enhancement in the rate and quality of wound closure both clinically and histologically relative to controls. Taken together, these results identify FL2 as a promising therapeutic target to promote the regeneration and repair of cutaneous wounds.Journal of Investigative Dermatology advance online publication, 9 April 2015; doi:10.1038/jid.2015.94.

Journal of Investigative Dermatology, 2015

Nano letters, Jan 13, 2010

We report the first observation of linear magnetoresistance (LMR) in multilayer epitaxial graphen... more We report the first observation of linear magnetoresistance (LMR) in multilayer epitaxial graphene grown on SiC. We show that multilayer epitaxial graphene exhibits large LMR from 2.2 K up to room temperature and that it can be best explained by a purely quantum mechanical model. We attribute the observation of LMR to inhomogeneities in the epitaxially grown graphene film. The large magnitude of the LMR suggests potential for novel applications in areas such as high-density data storage and magnetic sensors and actuators.

PLOS One, 2009

Staphylococcus aureus (SA) is a leading cause of a diverse spectrum of bacterial diseases, includ... more Staphylococcus aureus (SA) is a leading cause of a diverse spectrum of bacterial diseases, including abscesses. Nitric oxide (NO) is a critical component of the natural host defense against pathogens such as SA, but its therapeutic applications have been limited by a lack of effective delivery options. We tested the efficacy of a NO-releasing nanoparticle system (NO-np) in methicillin-resistant SA

Biomaterials, 2010

The use of indwelling medical devices (e.g. pacemakers, prosthetic joints, catheters, etc) contin... more The use of indwelling medical devices (e.g. pacemakers, prosthetic joints, catheters, etc) continues to increase, yet these devices are all too often complicated by infections with biofilm-forming microbes with increased resistance to antimicrobial agents and host defense mechanisms. We investigated the ability of chitosan, a polymer isolated from crustacean exoskeletons, to damage biofilms formed by the pathogenic fungus Cryptococcus neoformans.

2009 International Semiconductor Device Research Symposium, ISDRS '09, 2009

Journal of Nanomaterials, 2008

Page 1. Hindawi Publishing Corporation Journal of Nanomaterials Volume 2008, Article ID 782930, 7... more Page 1. Hindawi Publishing Corporation Journal of Nanomaterials Volume 2008, Article ID 782930, 7 pages doi:10.1155/2008/782930 Research Article Growth and Magnetic Properties of Polycrystalline Self-Assembled Bifurcated Co Nanowires ...

International journal of dermatology, Jan 29, 2014

The expansion of mobile technology and coverage has unveiled new means for delivering medical car... more The expansion of mobile technology and coverage has unveiled new means for delivering medical care to isolated and resource-poor communities. Teledermatology, or dermatology consultation from a distance using technology, is gaining greater acceptance among physicians and patients. To evaluate feasibility and cost of a smartphone-based teledermatology consult service utilizing a designated medical student proxy to facilitate all consults on site, and to evaluate the service's effect upon diagnosis and management. An IRB-approved smartphone-based teledermatology consult service was established to serve two rural communities in the developing world: Kisoro, Uganda, and Lake Atitlán, Guatemala. Fourth-year medical students were recruited as proxies for each site, responding to consults by local doctors and transmitting photographs and clinical information via a smartphone application to a dermatology resident and attending in the USA over an encrypted website. At the Ugandan site, w...

International Journal of Nanoscience, 2010

We demonstrate Co, Fe, and Ni encapsulated polyaniline (PAni) nanotubes using a three-step anodiz... more We demonstrate Co, Fe, and Ni encapsulated polyaniline (PAni) nanotubes using a three-step anodization and electrodeposition process. The electrodeposition process is used to create the tubes, as well as the wires, in a highly reliable manner. The metal-filled PAni structures ...

Proceedings of the National Academy of Sciences, 2002

Virulence

Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, it... more Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine abscess model and compared with vancomycin. All treatment arms accelerated abscess clearance clinically, histologically, and by microbiological assays on both days 4 and 7 following infection. However, abscesses treated with NO-np via either route demonstrated a more substantial, statistically significant decrease in bacterial survival based on colony forming unit assays and histologically revealed less inflammatory cell infiltration and preserved muscular architecture. These data suggest that the NO...

Nanomedicine : nanotechnology, biology, and medicine, Jan 13, 2017

Systemic therapies are preferred for treating dermal dermatophytosis due to inadequate penetratio... more Systemic therapies are preferred for treating dermal dermatophytosis due to inadequate penetration of topical agents. However, systemic antifungals are associated with off-target effects and limited tissue penetration, and antimicrobial resistance is a growing concern. To address this, we investigated topical nitric oxide-releasing nanoparticles (NO-np), which have been used against superficial fungal infections and bacterial abscesses. In addition to enhanced penetration and permeation conferred by nanoparticles, nitric oxide, a broad-spectrum multi-mechanistic antimicrobial agent, offers decreased likelihood of resistance development. In the current study, NO-np inhibited Trichophyton rubrum in vitro, as well as in a murine model of dermal dermatophytosis. In mice, NO-np reduced fungal burden after three days, with complete clearance after seven. Furthermore, NO-np decreased tissue IL-2, 6, 10 and TNFα, indicating earlier attenuation of the host inflammatory response and decreased...

The Journal of investigative dermatology, Jan 14, 2015

Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 inflammasome was recently h... more Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. Nitric oxide (NO), a potent biological messenger, has documented broad-spectrum antimicrobial and immunomodulatory properties. To harness these characteristics to target acne, we utilized an established nanotechnology capable of generating/releasing nitric oxide over time (NO-np). P. acnes was found to be highly sensitive to all concentrations of NO-np tested, though human keratinocyte, monocyte, and embryonic zebra fish assays revealed no cytotoxicity. NO-np significantly suppressed IL-1β, TNF-α, IL-8 and IL-6 from human monocytes and IL-8 and IL-6 from human keratinocytes respectively. Importantly, silencing of NLRP3 expression by small interfering RNA did not limit NO-np inhibition of IL-1 β secretion from monocytes, and neither TNF-α, nor ...

Frontiers in microbiology, 2015

Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect a... more Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect areas rich in keratin such as hair, nails, and skin. Significantly, there are increasing rates of antimicrobial resistance among dermatophytes, especially for Trichophyton rubrum, the most frequent etiologic agent worldwide. Hence, investigators have been developing new therapeutic approaches, including photodynamic treatment. Photodynamic therapy (PDT) utilizes a photosensitive substance activated by a light source of a specific wavelength. The photoactivation induces cascades of photochemicals and photobiological events that cause irreversible changes in the exposed cells. Although photodynamic approaches are well established experimentally for the treatment of certain cutaneous infections, there is limited information about its mechanism of action for specific pathogens as well as the risks to healthy tissues. In this work, we have conducted a comprehensive review of the current knowle...

The Journal of chemical physics, Jan 21, 2007

Several theoretical models have been formulated to explain the growth of porous structures in ano... more Several theoretical models have been formulated to explain the growth of porous structures in anodized alumina. Using some basic assumptions, these models predict the size and shape of the pores in the anodic porous alumina as functions of pH and voltage. Additionally, they address issues of stability in the pore growth. In this work, we have carried out a systematic experimental investigation to study the stability phase diagram as a function of pH and applied voltage. We also obtain the dependence of pore dimensions on the pH, voltage, and acid type. Based on our results, and insight gained from recent chemical analysis of the porous alumina anodization process, we conclude that the models must include an appropriate weighting factor to account for the oxidation and dissolution mechanism during the pore formation.

Journal of Investigative Dermatology, 2015

Wound healing is a complex process driven largely by the migration of a variety of distinct cell ... more Wound healing is a complex process driven largely by the migration of a variety of distinct cell types from the wound margin into the wound zone. In this study, we identify the previously uncharacterized microtubule-severing enzyme, Fidgetin-like 2 (FL2), as a fundamental regulator of cell migration that can be targeted in vivo using nanoparticle-encapsulated small interfering RNA (siRNA) to promote wound closure and regeneration. In vitro, depletion of FL2 from mammalian tissue culture cells results in a more than twofold increase in the rate of cell movement, in part due to a significant increase in directional motility. Immunofluorescence analyses indicate that FL2 normally localizes to the cell edge, importantly to the leading edge of polarized cells, where it regulates the organization and dynamics of the microtubule cytoskeleton. To clinically translate these findings, we utilized a nanoparticle-based siRNA delivery platform to locally deplete FL2 in both murine full-thickness excisional and burn wounds. Topical application of FL2 siRNA nanoparticles to either wound type results in a significant enhancement in the rate and quality of wound closure both clinically and histologically relative to controls. Taken together, these results identify FL2 as a promising therapeutic target to promote the regeneration and repair of cutaneous wounds.Journal of Investigative Dermatology advance online publication, 9 April 2015; doi:10.1038/jid.2015.94.

Journal of Investigative Dermatology, 2015

Nano letters, Jan 13, 2010

We report the first observation of linear magnetoresistance (LMR) in multilayer epitaxial graphen... more We report the first observation of linear magnetoresistance (LMR) in multilayer epitaxial graphene grown on SiC. We show that multilayer epitaxial graphene exhibits large LMR from 2.2 K up to room temperature and that it can be best explained by a purely quantum mechanical model. We attribute the observation of LMR to inhomogeneities in the epitaxially grown graphene film. The large magnitude of the LMR suggests potential for novel applications in areas such as high-density data storage and magnetic sensors and actuators.

PLOS One, 2009

Staphylococcus aureus (SA) is a leading cause of a diverse spectrum of bacterial diseases, includ... more Staphylococcus aureus (SA) is a leading cause of a diverse spectrum of bacterial diseases, including abscesses. Nitric oxide (NO) is a critical component of the natural host defense against pathogens such as SA, but its therapeutic applications have been limited by a lack of effective delivery options. We tested the efficacy of a NO-releasing nanoparticle system (NO-np) in methicillin-resistant SA

Biomaterials, 2010

The use of indwelling medical devices (e.g. pacemakers, prosthetic joints, catheters, etc) contin... more The use of indwelling medical devices (e.g. pacemakers, prosthetic joints, catheters, etc) continues to increase, yet these devices are all too often complicated by infections with biofilm-forming microbes with increased resistance to antimicrobial agents and host defense mechanisms. We investigated the ability of chitosan, a polymer isolated from crustacean exoskeletons, to damage biofilms formed by the pathogenic fungus Cryptococcus neoformans.

2009 International Semiconductor Device Research Symposium, ISDRS '09, 2009

Journal of Nanomaterials, 2008

Page 1. Hindawi Publishing Corporation Journal of Nanomaterials Volume 2008, Article ID 782930, 7... more Page 1. Hindawi Publishing Corporation Journal of Nanomaterials Volume 2008, Article ID 782930, 7 pages doi:10.1155/2008/782930 Research Article Growth and Magnetic Properties of Polycrystalline Self-Assembled Bifurcated Co Nanowires ...

International journal of dermatology, Jan 29, 2014

The expansion of mobile technology and coverage has unveiled new means for delivering medical car... more The expansion of mobile technology and coverage has unveiled new means for delivering medical care to isolated and resource-poor communities. Teledermatology, or dermatology consultation from a distance using technology, is gaining greater acceptance among physicians and patients. To evaluate feasibility and cost of a smartphone-based teledermatology consult service utilizing a designated medical student proxy to facilitate all consults on site, and to evaluate the service's effect upon diagnosis and management. An IRB-approved smartphone-based teledermatology consult service was established to serve two rural communities in the developing world: Kisoro, Uganda, and Lake Atitlán, Guatemala. Fourth-year medical students were recruited as proxies for each site, responding to consults by local doctors and transmitting photographs and clinical information via a smartphone application to a dermatology resident and attending in the USA over an encrypted website. At the Ugandan site, w...

International Journal of Nanoscience, 2010

We demonstrate Co, Fe, and Ni encapsulated polyaniline (PAni) nanotubes using a three-step anodiz... more We demonstrate Co, Fe, and Ni encapsulated polyaniline (PAni) nanotubes using a three-step anodization and electrodeposition process. The electrodeposition process is used to create the tubes, as well as the wires, in a highly reliable manner. The metal-filled PAni structures ...

Proceedings of the National Academy of Sciences, 2002