The prostate in women: an updated histological and immunohistochemical profile of the female periurethral glands and their relationship to an implanted midurethral sling

Tomalty, D; Giovannetti, O; Gaudet, D.; Clohosey, Diandra; Harvey, Marie-Andrée; Johnston, Shawna; Komisaruk, Barry R.; Hannan, Johanna L.; Goldstein, S.; Goldstein, Irwin; Adams, Michael

doi:10.1093/jsxmed/qdac046

Cited by 6 publications

(3 citation statements)

References 79 publications

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“…Furthermore, regions of microscopic innervation often contain a complex of nerve fiber types, including autonomic and sensory nerve fibers (Giovannetti et al, 2021 ; Karam, Moudouni, et al, 2005 ; Moszkowicz et al, 2011 ). Histology and IHC are commonly employed to help further clarify patterns of microscopic innervation and to distinguish between nerve types (Giovannetti et al, 2021 ; Tomalty, Giovannetti, Gaudet, et al, 2023 ). There are limitations to these approaches, however.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of human peripheral nerves using desorption electrospray ionization mass spectrometry imaging

et al. 2023

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Desorption electrospray ionization mass spectrometry imaging (DESI‐MSI) is a molecular imaging method that can be used to elucidate the small‐molecule composition of tissues and map their spatial information using two‐dimensional ion images. This technique has been used to investigate the molecular profiles of variety of tissues, including within the central nervous system, specifically the brain and spinal cord. To our knowledge, this technique has yet to be applied to tissues of the peripheral nervous system (PNS). Data generated from such analyses are expected to advance the characterization of these structures. The study aimed to: (i) establish whether DESI‐MSI can discriminate the molecular characteristics of peripheral nerves and distinguish them from surrounding tissues and (ii) assess whether different peripheral nerve subtypes are characterized by unique molecular profiles. Four different nerves for which are known to carry various nerve fiber types were harvested from a fresh cadaveric donor: mixed, motor and sensory (sciatic and femoral); cutaneous, sensory (sural); and autonomic (vagus). Tissue samples were harvested to include the nerve bundles in addition to surrounding connective tissue. Samples were flash‐frozen, embedded in optimal cutting temperature compound in cross‐section, and sectioned at 14 μm. Following DESI‐MSI analysis, identical tissue sections were stained with hematoxylin and eosin. In this proof‐of‐concept study, a combination of multivariate and univariate statistical methods was used to evaluate molecular differences between the nerve and adjacent tissue and between nerve subtypes. The acquired mass spectral profiles of the peripheral nerve samples presented trends in ion abundances that seemed to be characteristic of nerve tissue and spatially corresponded to the associated histology of the tissue sections. Principal component analysis (PCA) supported the separation of the samples into distinct nerve and adjacent tissue classes. This classification was further supported by the K‐means clustering analysis, which showed separation of the nerve and background ions. Differences in ion expression were confirmed using ANOVA which identified statistically significant differences in ion expression between the nerve subtypes. The PCA plot suggested some separation of the nerve subtypes into four classes which corresponded with the nerve types. This was supported by the K‐means clustering. Some overlap in classes was noted in these two clustering analyses. This study provides emerging evidence that DESI‐MSI is an effective tool for metabolomic profiling of peripheral nerves. Our results suggest that peripheral nerves have molecular profiles that are distinct from the surrounding connective tissues and that DESI‐MSI may be able to discriminate between nerve subtypes. DESI‐MSI of peripheral nerves may be a valuable technique that could be used to improve our understanding of peripheral nerve anatomy and physiology. The ability to utilize ambient mass spectrometry techniques in real time could also provide an unprecedented advantage for surgical decision making, including in nerve‐sparing procedures in the future.

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Section: Discussionmentioning

confidence: 99%

Molecular characterization of human peripheral nerves using desorption electrospray ionization mass spectrometry imaging

et al. 2023

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“…The vulvoscopic examination was performed in a standardized manner, from lateral to medial and from external to internal visualization at every study visit, including cotton-tipped swabbed testing of the vestibule. Detailed examination of the labia majora, labia minora, vestibule, clitoris, urethral meatus, vagina, and periurethral anterior wall prostate 22 , 23 was performed at 4× magnification with a ZoomScope vulvoscope (Wallach Surgical Devices) with an attached foot pedal–controlled EOS XSi Digital SLR camera (Cannon) that was linked to an LED monitor, allowing the participant and the health care provider to observe vulvoscopic findings concomitantly in real time.…”

Section: Methodsmentioning

confidence: 99%

Vestibular tissue changes following administration of intravaginal prasterone: a vulvoscopic open-label pilot study in menopausal women with dyspareunia

Goldstein¹,

Goldstein

Kim³

2023

Sexual Medicine

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Background Prasterone, an intravaginal dyspareunia treatment in menopausal women, improves vaginal health through intracellular conversion of dehydroepiandrosterone into androgens and estrogens. Phase 3 trials for prasterone showed significant improvement in vaginal tissue health and reduction of pain. Aim To assess vestibular changes with daily use of intravaginal prasterone in menopausal women with moderate to severe dyspareunia. Methods This open-label prospective pilot study was conducted over 20 weeks. It included 11 menopausal women (median age, 56 years) who were treated daily with intravaginal inserts of 6.5-mg prasterone and assessed monthly. During vulvoscopy, vestibular pain was assessed by cotton-tipped swab testing, and vestibular and vaginal health was independently assessed with the Visual Scale (VS). In addition, vulvoscopic photographs were obtained and assessed via the Vulvoscopic Genital Tissue Appearance (VGTA) scale to evaluate overall genital tissue health. Mean changes from baseline for genital tissue health and pain assessments were analyzed by repeated measures 1-way analysis of variance, followed by a Dunnett post hoc test. Sexual event diaries were completed and adverse events recorded. Outcomes Outcomes included indices of genital tissue health: pain assessment by cotton-tipped swab testing, VS of the vestibule and vagina, VGTA, and sexual event diary. Results Aggregate scores from the cotton-tipped swab test progressively improved, reaching statistical significance at week 16, which was maintained through week 20 (−7.27, P = .019). VS scores significantly improved from baseline by week 4 and were maintained through week 20 for the vestibule (−3.00, P = .004) and vagina (−4.00, P = .002). An overall 1607 vulvoscopic photographs were examined; all showed reduction in vestibular erythema and pallor at the end of the study. The mean change from baseline at week 20 for the VGTA score was −7.9 (P = .0016). Intercourse associated with pain was reduced from 81.3% of initiated events during the first month of the study to 8.3% during the last month. Sexual activities that were discontinued due to discomfort were reduced from 45.8% to 6.3%. No prasterone-related serious adverse events were reported. Clinical Implications Prasterone, a safe and effective intravaginal hormone treatment, significantly improves vestibular health parameters. Strengths and Limitations Strengths are the prospective study design and the use of multiple outcome measures to assess vestibular tissue health and pain associated with sexual activity. Limitations are the small study cohort and use of nonvalidated outcome measures. Conclusion Our findings suggest that intravaginal prasterone exerts biologic activity on the androgenic endodermal vestibule, as the medication passes from vagina to vestibule, resulting in amelioration of pain associated with sexual activity.

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“…While the implication of NGF and its receptors, TrkA and p75NTR (referred to as the NGF system) in CNS autoimmune neuroinflammation is not fully elucidated, the necessity of designing nerve growth factor (NGF) analogues to suppress pain signal transduction mediated by the p75NTR-NGF-TrkA complex arises from the intricate and multifaceted nature of the neurotrophic signaling pathways involved in CNS autoimmune neuroinflammation [29][30][31][32][33][34]. Since native NGF plays a pivotal role in both promoting neuronal survival and contributing to pain sensitization through its interactions with the p75NTR and TrkA receptors, the delicate balance between these contrasting effects underscores the need for targeted interventions that selectively modulate the signaling cascade to alleviate pain without compromising essential neurotrophic functions [35][36][37][38].…”

Section: Introductionmentioning

confidence: 99%

Designing Nerve Growth Factor Analogues to Suppress Pain Signal Transduction Mediated by the p75NTR-NGF-TrkA Complex: A Structural and Biophysical Perspective

2024

Preprint

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As a key mediator of chronic pain, neurotrophin nerve growth factor (NGF) binds to two neurotrophin receptors: p75 neurotrophin receptor (p75NTR) and tyrosine kinase receptor A (TrkA). The formation of the p75NTR-NGF-TrkA complex is implicated in the potentiation of chronic pain signals, making it an attractive target for therapeutic explorations. NGF analogues and monoclonal antibodies (mAbs) targeting NGF represent two distinct approaches in modulating the intricate signaling pathways involved in pain transduction mediated by the p75NTR-NGF-TrkA complex. While NGF analogues offer the advantage of tailored design to fine-tune neurotrophic responses, monoclonal antibodies provide a more systemic and comprehensive blockade of NGF, inhibiting its interactions with both p75NTR and TrkA receptors. However, the use of mAbs may pose challenges related to potential side effects and interference with the physiological functions of NGF. As a result, balancing the benefits and drawbacks of the two approaches is critical for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain. In this study, therefore, a novel structural and biophysical approach was employed for the design of NGF analogues to suppress p75NTR-NGF-TrkA-related chronic pain signaling. Employing high-throughput structural modeling and biophysics-based intermolecular binding affinity calculations, this article for the first time puts forward a set of NGF analogues, including in particular NGF analogues with four site-specific mutations, for whose dimerizations the K d at 37 ◦C were reduced by three orders of magnitude (from 10-9 M to 10-6 M) compared to the K d at 37 ◦C for the dimerization of native NGFs. Overall, the integration of structural and biophysical perspectives enhances our understanding of the rational design of NGF analogues as promising candidates for the development of NGF-targeted analgesic therapies, which balances the benefits and drawbacks of anti-NGF antibodies and NGF analogues for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain.

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The prostate in women: an updated histological and immunohistochemical profile of the female periurethral glands and their relationship to an implanted midurethral sling

Cited by 6 publications

References 79 publications

Molecular characterization of human peripheral nerves using desorption electrospray ionization mass spectrometry imaging

Molecular characterization of human peripheral nerves using desorption electrospray ionization mass spectrometry imaging

Vestibular tissue changes following administration of intravaginal prasterone: a vulvoscopic open-label pilot study in menopausal women with dyspareunia

Designing Nerve Growth Factor Analogues to Suppress Pain Signal Transduction Mediated by the p75NTR-NGF-TrkA Complex: A Structural and Biophysical Perspective

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