Andrology : open access最新文献

Aims: Aging associated erectile dysfunction is characterized within the corpora by a progressive apoptosis of the smooth muscle cells and their replacement by collagen. Nitric oxide from iNOS has been shown to inhibit these histological changes in the corpora while PDE5 inhibitors as well as certain nutraceuticals such as ginger, paullinia cupana, muira puama and L-citrulline are known to enhance the effects of NO. We evaluated whether the daily oral administration for 2 months with a combination of ginger, paullinia cupana, muira puama and L-citrulline (COMP-4) can effectively delay the ongoing corporal fibrosis, smooth muscle cell apoptosis and cavernosal veno-occlusive dysfunction (CVOD) seen in middle aged rats similar to that seen with tadalafil.

Methods: 10 Month old Fisher 344 rats were treated or not for two months with COMP-4, tadalafil or a combination of tadalafil plus COMP-4. CVOD was determined by dynamic infusion cavernosometry. Penile sections of the corpora cavernosa were subjected to Masson trichrome staining to evaluate fibrosis and immunohistochemistry for desmin as a marker of smooth muscle content and inducible nitric oxide synthase (iNOS) followed by image analysis. Oxidative stress levels were determined by GSH/GSSG ratio in whole blood.

Results: a decline in the non-treated rat's erectile function is evident by 10-12 months of age and is accompanied by a decrease in the corporal smooth muscle content determined by desmin expression and an increase in corporal fibrosis. The daily treatment for two months with COMP-4 reverses this process by reducing systemic oxidative stress and increasing desmin and iNOS expression, similar to that seen with tadalafil or the combination of COMP-4 plus tadalafil.

Conclusion: An oral combination of ginger, muira puama, Paullinia cupana and L-citrulline seems to be as effective as daily PDE5 inhibitor therapy in either delaying or reversing the onset of the histological and functional characteristics of aging related erectile dysfunction.

Introduction: The objective of this work is to examine if sensory innervation impacts lower urinary tract symptoms (LUTS). Onabotulinum toxin A (BoNTA) has been used for the treatment of overactive and neurogenic bladder and as a treatment for LUTS secondary to benign prostatic hyperplasia (BPH). The mechanism of how BoNTA impacts LUTS/BPH is unclear. In rats, BoNTA injection causes prostate denervation, apoptosis and atrophy. In clinical trials reduced prostate size and LUTS are observed inconsistently, suggesting a neurologic component. We will examine if BoNTA treatment inhibits substance P production in sensory nerve fibers in the rat prostate.

Methods: Twenty Sprague Dawley rats were divided into four groups including 1X PBS (control, n=6), 2.5 units Onabotulinum toxin A (BoNTA, n=6), 5 units BoNTA (n=6) injected into both lobes of the ventral prostate (VP) and sham surgery (n=2). Rats were Euthanized after one week. Substance P and its receptor neurokinin 1 localization and quantification were performed by counting the number of stained neurons and nerve bundles, by semi-quantitative immunohistochemical analysis and by western analysis.

Results: Substance P was localized in neuronal axons and bundles in the stroma of the VP but not in the epithelium. Receptor neurokinin 1 was identified in neuronal bundles of the stroma and in columnar epithelium of the VP ducts. Substance P decreased ~90% after BoNTA treatment (p=0.0001) while receptor neurokinin 1 did not change by IHC (p=0.213) or Western (p=0.3675).

Conclusions: BoNTA treatment decreases substance P in the rat VP.

Introduction: Neuronal nitric oxide synthase (NOS-I) is significantly decreased with Cavernous Nerve (CN) injury in Erectile Dysfunction (ED) models. Increased apoptosis and collagen deposition accompany decreased NOS/CN injury, however these changes are typically attributed to the altered signaling of other factors, and a contribution of NOS in maintenance of urogenital structures has not previously been examined. Morphological changes in the corpora cavernosa occur at the same time as decreased NOS, suggesting a potential connection between decreased/inhibited NOS and morphological changes associated with ED. In this study we propose that NOS impacts urogenital morphology during development and will examine this hypothesis by NOS inhibition with L-NAME.

Methods: Primary outcomes were H&E, western and TUNEL to determine if penis, prostate and bladder morphology were altered with L-NAME treatment of Postnatal day 4 (P4) Sprague Dawley rats for 8 days. Tissue weight and immunohistochemical analysis for NOS were performed. Secondary evaluation of NOS-I regulation by Sonic Hedgehog (SHH) was examined by SHH inhibition in the pelvic ganglia (PG) and NOS-I protein was quantified by western in the PG/CN and penis. Nos abundance was quantified by RT-PCR during urogenital development and after CN injury.

Results: Apoptosis increased and penis, prostate and bladder morphology were altered with L-NAME. NOS inhibition decreased bladder weight 25%. SHH inhibition decreased NOS-I 35% in the PG/CN and 47% in the penis. Nos-III expression spiked within the first two weeks after birth in the penis but remained abundant in the adult. In the prostate, Nos-III was abundant immediately after birth and declined steadily with age. Nos-I expression in the PG/CN decreased sharply with CN injury and returned to baseline by 7 days.

Conclusions: NOS is required for normal urogenital development. Since NOS is decreased with ED, it may contribute to the abnormal morphology observed in ED patients and animal models.