Gwen Lagoda

Johns Hopkins Medicine, Baltimore, Maryland, United States

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Publications (46)104.01 Total impact

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    ABSTRACT: IntroductionErectile dysfunction is a major complication of radical prostatectomy, commonly associated with penile neuropathy. In animal models of peripheral nerve injury, glial growth factor-2 (GGF2), a member of the neuregulin family of growth factors, has neuroprotective and neurorestorative properties, but this potential has not been established after cavernous nerve (CN) injury.AimsThe effectiveness of GGF2 in preserving axonal integrity and recovering erectile function in a rat model of radical prostatectomy-associated CN injury.Methods Adult male Sprague-Dawley rats underwent bilateral CN crush injury (BCNI) or sham surgery. Rats were administered GGF2 (0.5, 5, or 15 mg/kg) or vehicle subcutaneously 24 hour pre and 24-hour post-BCNI, and once weekly for 5 weeks. Erectile function was assessed in response to electrical stimulation of the CN. CN survival was assessed by fluorogold retrograde axonal tracing in major pelvic ganglia (MPG). Unmyelinated axons in the CNs were quantitated by electron microscopy.Main Outcome MeasuresErectile function recovery, CN survival, and unmyelinated CN axon preservation in response to GGF2 treatment following BCNI.ResultsErectile function was decreased (P < 0.05) after BCNI, and it was improved (P < 0.05) by all doses of GGF2. The number of fluorogold-labeled cells in the MPG was reduced (P < 0.05) by BCNI and was increased (P < 0.05) by GGF2 (0.5 and 5 mg/kg). The percentage of denervated Schwann cells in the BCNI group was higher (P < 0.05) than that in the sham-treated group and was decreased (P < 0.05) in the GGF2-treated (5 mg/kg) BCNI group. In the BCNI + GGF2 (5 mg/kg) group, the unmyelinated fiber histogram demonstrated a rightward shift, indicating an increased number of unmyelinated axons per Schwann cell compared with the BCNI group.ConclusionsGGF2 promotes erectile function recovery following CN injury in conjunction with preserving unmyelinated CN fibers. Our findings suggest the clinical opportunity to develop GGF2 as a neuroprotective therapy for radical prostatectomy. Burnett AL, Sezen SF, Hoke A, Caggiano AO, Iaci J, Lagoda G, Musicki B, and Bella AJ. GGF2 is neuroprotective in a rat model of cavernous nerve injury-induced erectile dysfunction. J Sex Med **;**:**–**.
    Journal of Sexual Medicine 02/2015; 12(4). DOI:10.1111/jsm.12834 · 3.15 Impact Factor
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    ABSTRACT: The pathogenesis of diabetic erectile dysfunction (ED) includes neuropathy, but the molecular basis for neurogenic ED is incompletely understood. The RhoA/ROCK pathway has been implicated in diabetic neuropathy and in ED, but its role in diabetic neurogenic ED is not known.
    Journal of Sexual Medicine 06/2014; 11(9). DOI:10.1111/jsm.12613 · 3.15 Impact Factor
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    ABSTRACT: The cavernous nerves, which course along the surface of the prostate gland, are responsible for erectile function. Urologic surgeons are challenged in preserving these nerves during prostate cancer surgery, due to their microscopic nature and variable location among patients. Current intra-operative diagnostic methods for identifying, imaging, and preserving these delicate nerves during removal of a cancerous prostate gland remain sub-optimal. Our laboratory is focused on developing optical-based methods for detecting these nerves. This manuscript reviews progress in pre-clinical development of infrared optical nerve stimulation as a potential technique for identifying the cavernous nerves. Critical laser parameters for safe and reliable stimulation of the cavernous nerves, development of laser and fiber optic probe instrumentation, and novel approaches are presented.
    IEEE Journal of Selected Topics in Quantum Electronics 03/2014; 20(2):1-8. DOI:10.1109/JSTQE.2013.2293273 · 3.47 Impact Factor
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    ABSTRACT: Optical nerve stimulation (ONS) has been commonly performed in the laboratory using high-power, pulsed, infrared (IR) lasers including Holmium:YAG, diode, and Thulium fiber lasers. However, the relatively high cost of these lasers in comparison with conventional electrical nerve stimulation (ENS) equipment may represent a significant barrier to widespread adoption of ONS. Optical stimulation of the prostate cavernous nerves (CN's) has recently been reported using lower cost, continuous-wave (CW), all-fiber-based diode lasers. This preliminary study describes further miniaturization and cost reduction of the ONS system in the form of a compact, lightweight, cordless, and inexpensive IR laser. A 140-mW, 1560-nm diode laser was integrated with a green aiming beam and delivery optics into a compact ONS system. Surface and subsurface ONS was performed in a total of 5 rats, in vivo, with measurement of an intracavernous pressure (ICP) response during CW laser irradiation for 30 s with a spot diameter of 0.7 mm. Short-term, CW ONS of the prostate CN's is feasible using a compact, inexpensive, batterypowered IR laser diode system. This ONS system may represent an alternative to ENS for laboratory studies, and with further development, a handheld option for ONS in the clinic to identify and preserve the CN's during prostate cancer surgery.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2014; DOI:10.1117/12.2043189 · 0.20 Impact Factor
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    ABSTRACT: To characterize transforming growth factor beta 1 (TGFβ1) and related signaling pathway proteins in a large cohort of human penile tissue (HPT) samples. HPT was collected from patients undergoing penile prosthesis implantation for erectile dysfunction (ED) and divided into the following 2 groups: postradical prostatectomy ED (RP-ED; n = 57) and organic ED (O-ED; n = 30). HPT from patients undergoing partial penectomy without ED was used as controls (CON; n = 6). Western blot analysis was performed to investigate the protein expressions of TGFβ1, thrombospondin 1 (TSP1; an activator of TGFβ1), fibronectin (an extracellular matrix glycoprotein induced by TGFβ1), and a family of transcriptional factors activated by TGFβ1 (Smad2, phospho-Smad2-serine-465/467 [pSmad2], Smad3, phospho-Smad3-serine-423/425 [pSmad3]). Expressions of TGFβ1 and TSP1 were significantly higher in RP-ED (P <.05) and O-ED (P <.05) groups compared with that of the CON group and were not different between either ED groups. Expressions of Smad2, pSmad2, Smad3, pSmad3, and fibronectin were similar among all groups. Within the RP-ED group, a subgroup analysis showed that time from RP to penile prosthesis implantation was related to increased expression of pSmad2 (P <.05), and previous history of intracavernosal injection was related to increased expression of TGFβ1 (P <.05). Our results demonstrate that TSP1- and TGFβ1-dependent fibrotic changes occur in penile tissue in patients with ED regardless of etiology. The unchanged expression of the Smad transcriptional factors may be reconciled by a Smad-independent downstream signaling pathway transmitting TGFβ1 signals.
    Urology 10/2013; 82(4):975.e1-6. DOI:10.1016/j.urology.2013.06.042 · 2.13 Impact Factor
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    ABSTRACT: We evaluated the therapeutic potential of a sustained nitric oxide (NO)-releasing compound to correct the molecular hallmarks and pathophysiology of priapism, an important but poorly characterized erectile disorder. 1,5-Bis-(dihexyl-N-nitrosoamino)-2,4-dinitrobenzene (C6') and an inactive form of the compound [1,5-bis-(dihexylamino)-2,4-dinitrobenzene (C6)] were tested in neuronal cell cultures and penile lysates for NO release (Griess assay) and biological activity (cGMP production). The effect of local depot C6' or C6 was evaluated in mice with a priapic phenotype due to double neuronal and endothelial NO synthase deletion (dNOS(-/-)) or human sickle hemoglobin transgenic expression (Sickle). Changes in NO signaling molecules and reactive oxygen species (ROS) surrogates were assessed by Western blot. The physiological response after C6' treatment was assessed using an established model of electrically stimulated penile erection. C6' generated NO, increased cGMP, and dose dependently increased NO metabolites. C6' treatment reversed abnormalities in key penile erection signaling molecules, including phosphodiesterase type 5, phosphorylated endothelial nitric oxide synthase, and phosphorylated vasodilator-stimulated phosphoprotein. In Sickle mice, C6' also attenuated the increased ROS markers gp91(phox), 4-hydroxynonenal, and 3-nitrotyrosine. Finally, C6' corrected the excessive priapic erection response of dNOS(-/-) mice. Exogenous sustained NO release from C6' corrects pathological erectile signaling in mouse models of priapism and suggests novel approaches to human therapy.-Lagoda, G., Sezen, S. F., Hurt, K. J., Cabrini, M. R., Mohanty, D. K., Burnett, A. L. Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism.
    The FASEB Journal 09/2013; 28(1). DOI:10.1096/fj.13-228817 · 5.48 Impact Factor
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    ABSTRACT: To optimize the infrared laser wavelength and optical nerve stimulation (ONS) parameters for both deep and rapid subsurface cavernous nerve (CN) stimulation in a rat model, in vivo. A 150-mW, 1490-nm diode laser providing an optical penetration depth (OPD) of 518 μm in water was operated in continuous-wave mode during stimulation of the CNs in 8 rats for 15 seconds irradiation time through a custom-built, single-mode fiber optic probe capable of producing a collimated, 1-mm diameter laser beam. Successful ONS was judged by an intracavernous pressure response in the rat penis. Subsurface ONS at 1490 nm was also compared with previous studies using 1455 nm and 1550 nm near-infrared diode laser wavelengths. Subsurface ONS of the rat CN was successful through fascia layers with a thickness up to 380 μm using an incident laser power of ∼50 mW. Intracavernous pressure response times as short as 4.6 ± 0.2 seconds were recorded using higher laser powers below the nerve damage threshold. The 1490-nm diode laser represents a compact, low cost, high power, and high quality infrared light source for use in ONS. This wavelength provides deeper penetration than 1455-nm diode laser and more rapid and efficient nerve stimulation than 1550-nm diode laser.
    Urology 08/2013; 82(4). DOI:10.1016/j.urology.2013.06.031 · 2.13 Impact Factor
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    ABSTRACT: Optical nerve stimulation (ONS) may be useful as a diagnostic tool for intraoperative identification and preservation of the prostate cavernous nerves (CN), responsible for erectile function, during prostate cancer surgery. Successful ONS requires elevating the nerve temperature to within a narrow range (∼42 to 47°C) for nerve activation without thermal damage to the nerve. This preliminary study explores a prototype temperature-controlled optical nerve stimulation (TC-ONS) system for maintaining a constant (±1°C) nerve temperature during short-term ONS of the rat prostate CNs. A 150-mW, 1455-nm diode laser was operated in continuous-wave mode, with and without temperature control, during stimulation of the rat CNs for 15 to 30 s through a fiber optic probe with a 1-mm-diameter spot. A microcontroller opened and closed an in-line mechanical shutter in response to an infrared sensor, with a predetermined temperature set point. With TC-ONS, higher laser power settings were used to rapidly and safely elevate the CNs to a temperature necessary for a fast intracavernous pressure response, while also preventing excessive temperatures that would otherwise cause thermal damage to the nerve. With further development, TC-ONS may provide a rapid, stable, and safe method for intraoperative identification and preservation of the prostate CNs.
    Journal of Biomedical Optics 06/2013; 18(6):67001. DOI:10.1117/1.JBO.18.6.067001 · 2.75 Impact Factor
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    ABSTRACT: Optical nerve stimulation (ONS) is being explored for identification and preservation of the cavernous nerves (CN), responsible for erectile function, during prostate cancer surgery. This study compares three pulsed infrared lasers to determine whether differences in spectral linewidth and/or temporal pulse profile influence successful ONS of CN. Infrared laser radiation from the Capella diode laser (1873 nm, 5 ms, 10 Hz), Thulium fiber laser (TFL) (1873 nm, 5 ms, 10 Hz), and solid-state Holmium:YAG laser (2120 nm, 200 μs, 5 Hz) were transmitted through 400-μm-corediameter optical fibers, producing a 1-mm-diameter-spot on the nerve surface. Successful ONS was judged by an intracavernous pressure (ICP) response in the penis (n =10 rats) during a total stimulation time of 30 s. The narrow linewidth TFL (Δλ ~ 0.5 nm) and broad linewidth Capella laser (Δλ ~ 12 nm) performed similarly, producing ICP responses with a threshold radiant exposure of ~ 0.45 J/cm2, and ICP response times of 12-17 s, while the Holmium laser stimulated at ~ 0.59 J/cm2, and ICP response times of about 14-28 s. All three lasers demonstrated successful ONS of CN. ICP response time was dependent on the rate of energy deposition into the CN, rather than linewidth or temporal pulse profile.
    Conference on Photonic Therapeutics and Diagnostics IX; 03/2013
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    ABSTRACT: Successful identification of the cavernous nerves (CN’s) during radical prostatectomy requires detection of the CN’s through a thin layer of overlying fascia. This study explores the 1490 nm infrared (IR) diode laser wavelength for rapid and deep subsurface CN stimulation in a rat model, in vivo. A 150-mW, 1490-nm diode laser providing an optical penetration depth of ~ 520 μm was used to stimulate the CN’s in 8 rats through a single mode fiber optic probe with 1-mm-diameter spot and 15 s irradiation time. Successful ONS was judged by an intracavernous pressure response (ICP) in the rat penis. Subsurface ONS at 1490 nm was also compared with previous studies using 1455 and 1550 nm IR diode laser wavelengths. ONS was observed through fascia layers up to 380 μm thick using an incident laser power of ~ 50 mW. ICP response times as short as 4.6 ± 0.2 s were recorded using higher laser powers bust still below the nerve damage threshold. The 1490-nm diode laser represents a compact, low cost, high power, and high quality infrared light source for use in ONS. This wavelength provides deeper optical penetration than 1455 nm and more rapid and efficient nerve stimulation than 1550 nm.
    Conference on Photonic Therapeutics and Diagnostics IX; 03/2013
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    ABSTRACT: Successful identification and preservation of the cavernous nerves (CN), which are responsible for sexual function and vulnerable to damage during prostate cancer surgery, will require subsurface detection of the CN's beneath a thin fascia layer. This study explores the feasibility of optical nerve stimulation (ONS) in the rat with a fascia layer placed over the CN. Two near-infrared diode lasers with wavelengths of 1455 and 1550 nm were operated in continuous-wave mode for stimulation of the CN in 8 rats, in vivo. Successful ONS was confirmed by an intracavernous pressure (ICP) response in the rat penis at 1455 nm through fascia with a thickness up to 110 μm and at 1550 nm through fascia with a thickness up to 450 μm. Higher incident laser power was required to produce an ICP response as fascia thickness was increased. Also, weaker and slower ICP responses were observed as fascia thickness was increased. Subsurface ONS of the rat CN at a depth of 450 μm using a 1550 nm laser is feasible as an intermediate step towards developing ONS as an intra-operative diagnostic tool for identification and preservation of the cavernous nerves during prostate cancer surgery. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
    Journal of Biophotonics 10/2012; 5(10):793-800. DOI:10.1002/jbio.201100134 · 3.86 Impact Factor
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    ABSTRACT: PURPOSE: Priapism is a vasculopathy occurring in approximately 40% of patients with SCD. Mouse models have suggested that dysregulated NOS and RhoA/ROCK signaling as well as increased oxidative stress may contribute to mechanisms of SCD-associated priapism. We examined changes in protein expressions of NOS and ROCK signaling pathways and a source of oxidative stress, NADPH oxidase, in penile erectile tissue from patients with priapism histories, etiologically related and unrelated to SCD. MATERIALS AND METHODS: Human penile erectile tissue was obtained from patients with SCD-associated priapism (SCD, n=5) and priapism of other etiologies (non-SCD, n=6) during non-emergent penile prosthesis surgery for ED or priapism management and urethroplasty, and from control patients without priapism histories (Control, n=5) during penectomy for penile cancer. Samples were collected, immediately placed in cold buffer and then frozen in liquid nitrogen. Expressions of PDE5, eNOS, nNOS, iNOS, RhoA, ROCK1, ROCK2, p47(phox), p67(phox), gp91(phox) and β-actin were determined by Western blot analysis and NO amount was measured using the Griess reaction. RESULTS: In the SCD group, PDE5 (p<0.05), eNOS (p<0.01) and RhoA (p<0.01) expressions were significantly decreased while gp91(phox) (p<0.05) expression was significantly increased compared to Control group values. In the non-SCD group, eNOS (p<0.05), ROCK1 (p<0.05) and p47(phox) (p<0.05) expressions were significantly decreased compared to Control group values. Total NO levels were not significantly different across study groups. CONCLUSIONS: The mechanisms of SCD-associated priapism in the human penis may involve dysfunctional NOS and ROCK signaling and increased oxidative stress associated with NADPH oxidase-mediated signaling.
    The Journal of urology 09/2012; 189(2). DOI:10.1016/j.juro.2012.08.198 · 3.75 Impact Factor
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    ABSTRACT: Successful identification and preservation of the cavernous nerves (CN), which are responsible for sexual function, during prostate cancer surgery, will require subsurface detection of the CN beneath a thin fascia layer. This study explores optical nerve stimulation (ONS) in the rat with a fascia layer placed over the CN. Two near-IR diode lasers (1455 nm and 1550 nm lasers) were used to stimulate the CN in CW mode with a 1-mm-diameter spot in 8 rats. The 1455 nm wavelength provides an optical penetration depth (OPD) of ~350 μm, while 1550 nm provides an OPD of ~1000 μm (~3 times deeper than 1455 nm and 1870 nm wavelengths previously tested). Fascia layers with thicknesses of 85 - 600 μm were placed over the CN. Successful ONS was confirmed by an intracavernous pressure (ICP) response in the rat penis at 1455 nm through fascia 110 μm thick and at 1550 nm through fascia 450 μm thick. Higher incident laser power was necessary and weaker and slower ICP responses were observed as fascia thickness was increased. Subsurface ONS of the rat CN at a depth of 450 μm using a 1550 nm laser is feasible.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2012; DOI:10.1117/12.905256 · 0.20 Impact Factor
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    ABSTRACT: Nitric oxide is the major neuronal mediator of penile erection but its role in erectile function status after cavernous nerve injury is uncertain. We determined the function of neuronal nitric oxide signaling in the pathobiology of erectile function recovery after partial cavernous nerve injury using genetic and pharmacological mouse experimental paradigms. Erectile function was evaluated in 5 to 7 wild-type and neuronal nitric oxide synthase-α knockout mice per group 1, 3 and 7 days after unilateral crush or sham injury, at day 7 in wild-type mice treated with the nitric oxide synthase inhibitor L-NAME (l-nitro arginine methyl ester) (Sigma-Aldrich®) at baseline and for 6 days after unilateral crush injury. Apoptosis in the penis was evaluated by Western blot analysis of p-Akt-S473, 3-nitrotyrosine and caspase-3 after bilateral crush injury. Intracavernous pressure was significantly decreased at 1, 3 and 7 days in wild-type mice but only at day 1 in knockout mice after unilateral crush injury compared with sham treatment values (p <0.05). L-NAME treated wild-type mice had improved erectile function compared with the vehicle treated group at day 7 after unilateral crush injury (p <0.05). In penes p-Akt-S473 was significantly decreased in vehicle treated (p <0.05) but not in L-NAME treated wild-type mice. In penes 3-nitrotyrosine was significantly decreased in L-NAME treated wild-type and vehicle treated knockout mice (p <0.05). Caspase-3 in penes was significantly increased in vehicle treated (p <0.05) but not in L-NAME treated wild-type mice and vehicle treated knockout mice. Neuronal nitric oxide signaling regulates erectile function recovery early after partial cavernous nerve injury, exerting an inhibitory role via the induction of apoptotic change in penile tissue. Therapeutic strategies to improve erectile function recovery after radical prostatectomy may consider targeting pathogenic sites of nitric oxide neurobiology.
    The Journal of urology 12/2011; 187(2):757-63. DOI:10.1016/j.juro.2011.09.146 · 3.75 Impact Factor
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    ABSTRACT: Immunophilin ligands such as FK506 (FK) preserve erectile function (EF) following cavernous nerve injury (CNI), although the precise mechanisms are unclear. We examined whether the thioredoxin (Trx) and glutathione (GSH) redox systems mediate this effect after CNI. To investigate the roles of Trx reductase 2 (TrxR2) and S-Nitrosoglutathione reductase (GSNOR) as antioxidative/nitrosative and antiapoptotic mediators of the neuroprotective effect of FK in the penis after CNI. Adult male rats, wild-type (WT) mice, and GSNOR deficient (GSNOR -/-) mice were divided into four groups: sham surgery (CN [cavernous nerves] exposure only) + vehicle; sham surgery + FK (5 mg/kg/day/rat or 2 mg/kg/day/mouse, for 2 days, subcutaneous); CNI + vehicle; and CNI + FK. At day 4 after injury, electrically stimulated changes in intracavernosal pressure (ICP) were measured. Penises were collected for Western blot analysis of TrxR2, GSNOR, and Bcl-2, and for immunolocalization of TrxR2 and GSNOR. EF assessment represented by maximal ICP and total ICP in response to electrical stimulation. Evaluation of protein expression levels and distribution patterns of antioxidative/nitrosative and antiapoptotic factors in penile tissue. EF decreased after CNI compared with sham surgery values in both rats (P < 0.01) and WT and GSNOR -/- mice (P < 0.05). FK treatment preserved EF after CNI compared with vehicle treatment in rats (P < 0.01) and WT mice (P < 0.05) but not in GSNOR -/- mice. In rats, GSNOR (P < 0.01) and Bcl-2 (P < 0.05) expressions were significantly decreased after CNI. FK treatment in CN-injured rats restored expression of GSNOR and upregulated TrxR2 (P < 0.001) and Bcl-2 (P < 0.001) expressions compared with vehicle treatment. Localizations of proteins in the penis were observed for TrxR2 (endothelium, smooth muscle) and for GSNOR (nerves, endothelium, smooth muscle). The neuroprotective effect of FK in preserving EF after CNI involves antioxidative/nitrosative and antiapoptotic mechanisms mediated, to some extent, by Trx and GSH systems.
    Journal of Sexual Medicine 12/2011; 8(12):3325-34. DOI:10.1111/j.1743-6109.2011.02500.x · 3.15 Impact Factor
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    ABSTRACT: Laser stimulation of the rat cavernous nerve (CN) recently has been demonstrated as an alternative to electrical stimulation for potential application in nerve mapping during nerve-sparing radical prostatectomy. Advantages include noncontact stimulation and improved spatial selectivity. Previous studies, however, have used large and/or expensive laser sources for stimulation. This study demonstrates the feasibility of optical stimulation of the rat CN, in vivo, using a compact, inexpensive all-single-mode fiberoptic system. A 1455-nm wavelength infrared diode laser beam was coupled into a 9-μm-core single-mode fiber for delivery through a 10F laparoscopic probe and used for laser stimulation of the CN in a total of eight rats, in vivo. Laser stimulation of the CN was observed at threshold temperatures of 41°C, with intracavernous pressure response times as short as 4 s, and magnitudes up to 50 mm Hg, compared with baselines of 10 mm Hg. This novel, all-single-mode-fiber laser nerve stimulation system introduces several advantages including: (1) lower cost laser; (2) more robust fiberoptic design, eliminating alignment and cleaning of bulk optical components; and (3) improved Gaussian spatial beam profile for simplified alignment of the laser beam with the nerve. With further development, laser nerve stimulation may be useful for identification and preservation of the CN during prostate cancer surgery.
    Journal of endourology / Endourological Society 09/2011; 25(11):1727-31. DOI:10.1089/end.2011.0172 · 2.10 Impact Factor
  • The Journal of Urology 04/2011; 185(4). DOI:10.1016/j.juro.2011.02.726 · 3.75 Impact Factor
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    ABSTRACT: Optical nerve stimulation (ONS) has recently been reported as a potential alternative to electrical nerve stimulation. Continuous-wave (CW) laser stimulation of the prostate cavernous nerves (CN) in a rat model, in vivo, has also been demonstrated in our previous studies. The objective of this study is to present a new all-single-mode-fiber configuration for ONS with the laser operating in CW mode for potential diagnostic applications. An infrared pigtailed single-mode diode laser (λ = 1455 nm) was used in this study for noncontact ONS. This new all-fiber approach introduces several advantages including: (1) a less expensive and more compact ONS system, (2) elimination of alignment of optical components, and (3) an improved spatial beam profile. Successful optical stimulation of the rat CN using this new design was observed after the CN reached a threshold temperature of ~ 41 °C with response times as short as 3 s. Upon further study, this configuration may be useful for identification and preservation of the cavernous nerves during prostate cancer surgery.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2011; DOI:10.1117/12.884988 · 0.20 Impact Factor
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    ABSTRACT: Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH(4)) on erectile function in the aged rats. Male Fischer 344 'young' (4-month-old) and 'aged' (19-month-old) rats were treated with a BH(4) precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED.
    International journal of impotence research 02/2011; 23(2):43-8. DOI:10.1038/ijir.2011.2 · 1.37 Impact Factor
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    ABSTRACT: Optical nerve stimulation has recently been developed as an alternative to electrical nerve stimulation. However, recent studies have focused primarily on pulsed delivery of the laser radiation and at relatively low pulse rates. The objective of this study is to demonstrate faster optical stimulation of the prostate cavernous nerves using continuouswave (CW) infrared laser radiation, for potential diagnostic applications. A Thulium fiber laser (lambda = 1870 nm) was used for non-contact optical stimulation of the rat prostate cavernous nerves, in vivo. Optical nerve stimulation, as measured by an intracavernous pressure (ICP) response in the penis, was achieved with the laser operating in either CW mode, or with a 5-ms pulse duration at 10, 20, 30, 40, 50, and 100 Hz. Successful optical stimulation was observed to be primarily dependent on a threshold nerve temperature (42-45 °C), not an incident fluence, as previously reported. CW optical nerve stimulation provides a significantly faster ICP response time using a laser with lower power output than pulsed stimulation. CW optical nerve stimulation may therefore represent an alternative mode of stimulation for intra-operative diagnostic applications where a rapid response is critical, such as identification of the cavernous nerves during prostate cancer surgery.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2011; DOI:10.1117/12.872876 · 0.20 Impact Factor

Publication Stats

574 Citations
104.01 Total Impact Points

Institutions

  • 2007–2015
    • Johns Hopkins Medicine
      • Department of Urology
      Baltimore, Maryland, United States
  • 2013
    • Harvard University
      Cambridge, Massachusetts, United States
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
  • 2006–2013
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2008–2010
    • University of North Carolina at Charlotte
      • Department of Physics & Optical Science
      Charlotte, NC, United States