Papers by Fabio Castiglione
Indonesian Journal of Urology, 2021
Objective: This study aimed to gives a perspective in CM-ADMSCs effect in urothelial bladder canc... more Objective: This study aimed to gives a perspective in CM-ADMSCs effect in urothelial bladder cancer viability. Material & Methods: Human bladder cell carcinoma type 5637 was used as the subject of this in vitro study. This study contains four different groups: untreated control group, Culture medium: hADMSCs with 1:1, 1:2, and 1:4 concentration group. Each group consists of 6 replications to prevent bias of the study. Viability was determined with MTT assay methods and evaluation performed after 48 h exposure of conditioned medium. Results: A post hoc test was conducted to analyze the data. The 5637 bladder cancer cell line demonstrated significantly decreased viability after exposure to culture medium: CM-hADMSCs 1:1 (p: 0.002) compared to the negative control group, but there are no significant differences in viability between the control groups with groups that were exposed to culture medium: CM-hADMSCs 1:2 and culture medium: CM-hADMSCs 1:4 with p: 0.480 and p: 0.060 respectivel...
Surgical Procedures for Core Urology Trainees, 2017
Current Urology Reports, 2017
Purpose of Review Due to the increasing numbers of radical prostatectomies (RP) performed for pro... more Purpose of Review Due to the increasing numbers of radical prostatectomies (RP) performed for prostate cancer, a substantial number of patients are now suffering from post-operative erectile dysfunction (ED). The aim of this study is to summarize the current literature on surgical techniques for managing post-prostatectomy erectile dysfunction. Recent Findings The PubMed database was searched for English-language articles published up to Jan 2017 using the following search terms: "prostatectomy AND erectile dysfunction", "prostatectomy AND penile prostheses", and "prostatectomy AND penile implants". All of the studies that evaluated medical treatment were excluded. In the last few decades, the understanding of the anatomy of the male pelvis and prostate has improved. This has led to significant changes in the nerve-sparing radical prostatectomy techniques, with the aim of preserving post-surgical erectile function (EF). In this scenario, the prostate vascular supply and the anatomy of the neurovascular bundles have a central role. Penile prosthesis implantation is considered the third-line treatment option for RP ED patients, and they have been reported to be a very successful treatment with the highest patient satisfaction rate. Summary Considering the failure of penile rehabilitation, and the lack of evidence for accessory pudendal artery (APA) preservation and nerve graft, nerve-sparing surgery and penile prostheses represent, today, the only methods to permanently and definitively preserve or erectile function after RP.
The journal of sexual medicine, 2018
Previously, we found that the neuropeptide galanin was strongly upregulated soon after bilateral ... more Previously, we found that the neuropeptide galanin was strongly upregulated soon after bilateral cavernous nerve injury (BCNI) and that galanin and its receptors were expressed in nitrergic erectile innervation. Galanin has been observed to exert neuroregenerative effects in dorsal root ganglion neurons, but evidence for these effects in the major pelvic ganglion (MPG) after BCNI is lacking. To evaluate the neurotropic effects of galanin receptor agonists and antagonists in vitro in nitrergic neurons and MPG and in vivo in rats after BCNI. Male Sprague-Dawley rats underwent BCNI and sham surgery. Organ culture and single-cell neuron culture of the MPG were performed. Osmotic pump treatment with the galanin agonist in vivo and measurement of erectile response to electrostimulation after BCNI, immunohistochemical localization of galanin and receptors in the human neurovascular bundle, and myographic analysis of rat corpus cavernosum smooth muscle relaxation to galanin receptor agonist...
BJU international, Jan 29, 2018
Previous studies have shown that the injection of adipose tissue-derived stem cells (ADSCs) into ... more Previous studies have shown that the injection of adipose tissue-derived stem cells (ADSCs) into the tunica albuginea (TA) during the active phase of the Peyronie's disease (PD) prevents the development of fibrosis and elastosis in the TA and corpus cavernosum The aim of this study was to investigate whether local injection of autologous adipose stromal vascular fraction (SVF) can prevent the development of fibrosis and elastosis in the TA using a rat model of acute phase of the Peyronie's disease (PD) METHODS: A total of 24 male 12-wk-old Sprague-Dawley rats were divided in three equal groups: sham, PD without treatment (TGFB) and PD treated with SVF (SVF) 1 day after disease induction. Sham rats underwent 2 injections of vehicle into the TA one day apart. TGFB rats underwent TGF- β1 injection and injection of vehicle one day later. SVF rats underwent TGF-β1 injection followed by SVF one day later. One month after treatment all rats underwent measurement of intracorporal pr...
European Urology Supplements, 2011
results: The trial was completed by 33 (97%) men. The mean IELT increased from pre-treatment valu... more results: The trial was completed by 33 (97%) men. The mean IELT increased from pre-treatment values of 28.5+22.1 and 32.4+24.7 seconds to 142.2+76.5 and 41.7+38.3 seconds post treatment respectively for CL spray and placebo (P<0.05 for treatment group), baseline mean CIPE scores 31+8 and 32+9 reached to 45+7 and 33+6 at 8-week treatment for CL spray and placebo, respectively (P<0.05 for treatment group). The differences between initial and post-treatment IIEF-5 values in both groups were statistically insignificant (32.5+1.5 and 32.5+1.0 vs. 31.6+3 and 32+0.6 in main and placebo groups, respectively, P>0,1). The most common observed side effect was nasal irritation in 3 patients in CL spray and 1 patient in placebo group, but it was transient and well tolerated. The other adverse effects occurred in 2 patients of CL spray group were dry month and headache (in last case this caused discontinuation of therapy). Conclusions: This study showed that CL spray was more efficacious than placebo and well tolerated. The common adverse reactions were mild and selflimited. Further studies with different groups of patients are necessary to draw final conclusions on the efficacy and safety of CL spray in PE.
Asian journal of andrology
animals and human beings. According to these results, overexpression of hKLK1 might counteract th... more animals and human beings. According to these results, overexpression of hKLK1 might counteract the effect of ROCK system and prevent the inevitable age-related fibrosis of the penis. Although the study showed a possible new target of the treatment of ED, the conclusions arising from this experiment are difficult to interpret. In our opinion, the conclusions of this study could have been affected by several limitations. First, we think that the evaluation of penile fibrosis, which represents the main endpoint of this study, may be not adequate. The authors performed a semiquantitative method, Masson's trichrome, for the evaluation of collagen content in the penis. In our opinion, a quantitative method like Western blot analysis for collagen and elastin content of the corpora cavernosa could be more accurate. 10,11 Second, the author stated in the conclusion that the fibrosis prevention is due to the inhibition of the ROCK pathway without investigating the effect of the hKLK1 on the NO system. NO represents the main actor of the penile erection mechanism and, additionally, it is well known for its antifibrotic properties. 1,5 More important, data suggest that effectors of the activated NO pathway may inhibit the ROCK pathway. Under this point of view, the activation of NO system may be responsible for the protective effects of hKLK. This aspect represents, in our opinion, the main limit of the study, especially because the same group had already shown, in a recently very similar study, that hKLK1 could play a preventive role in age-related erectile dysfunction by activation of the NO-cGMP pathway and inhibition of the RhoA-ROCK pathway. 12 Despite its limitations, this study adds valuable data to the literature suggesting that hKLK gene therapy can benefit patients with age-related ED by attenuating the penile fibrotic process. The question of how the activation of kallikrein system is able to prevent the age-related penile fibrosis needs to be addressed. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
International urogynecology journal, Jan 16, 2016
Bilateral pelvic nerve injury (BPNI) is a model of post-radical hysterectomy neuropraxia, a commo... more Bilateral pelvic nerve injury (BPNI) is a model of post-radical hysterectomy neuropraxia, a common sequela. This study assessed the time course of changes to detrusor autonomic innervation, smooth muscle (SM) content and cholinergic-mediated contraction post-BPNI. Female Sprague-Dawley rats underwent BPNI or sham surgery and were evaluated 3, 7, 14, and 30 days post-BPNI (n = 8/group). Electrical field-stimulated (EFS) and carbachol-induced contractions were measured. Gene expression was assessed by qPCR for muscarinic receptor types 2 (M2) and 3 (M3), collagen type 1α1 and 3α1, and SM actin. Western blots measured M2 and M3 protein expression. Bladder sections were stained with Masson's trichrome for SM content and immunofluorescence staining for nerve terminals expressing vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), and neuronal nitric oxide synthase (nNOS). Bilateral pelvic nerve injury caused larger bladders with less SM content and increased colla...
The journal of sexual medicine, 2017
Neurogenic erectile dysfunction is a common sequela of radical prostatectomy. The etiology involv... more Neurogenic erectile dysfunction is a common sequela of radical prostatectomy. The etiology involves injury to the autonomic cavernous nerves, which arise from the major pelvic ganglion (MPG), and subsequent neuroinflammation, which leads to recruitment of macrophages to the injury site. Currently, two macrophage phenotypes are known: neurotoxic M1 macrophages and neuroprotective M2 macrophages. To examine whether bilateral cavernous nerve injury (BCNI) in a rat model of erectile dysfunction would increase recruitment of neurotoxic M1 macrophages to the MPG. Male Sprague-Dawley rats underwent BCNI and the MPG was harvested at various time points after injury. The corpora cavernosa was used to evaluate tissue myographic responses to electrical field stimulation ex vivo. Quantitative real-time polymerase chain reaction was used to examine the gene expression of global macrophage markers, M1 macrophage markers, M2 macrophage markers, and cytokines and chemokines in the MPG. Mathematical...
Sexual Medicine Reviews, 2017
Introduction: Stem cells for sexual disorders are steadily being introduced into clinical trials.... more Introduction: Stem cells for sexual disorders are steadily being introduced into clinical trials. Two conditions of importance are the main target for this line of treatment, especially when regarding the wide array of translational and basic science highlighting the potential advantages of regenerative therapy: erectile dysfunction (ED) and more recently Peyronie disease (PD). Cellular therapy offers a treatment modality that might reverse disease progression. It would be used in a curative setting, in contrast to other pharmaceutical agents that are currently available. Aim: To review basic preclinical studies and recent clinical trials of stem cells on ED and PD. Methods: A search of the medical literature for the following terms was performed using PubMed: stem cells, cellular therapy, erectile dysfunction, Peyronie's disease, and clinical trial. Main Outcome Measures: A non-systematic narrative review and critical reflection on preclinical and clinical studies administering stem cells for ED and PD in animal models and human subjects. Results: Numerous studies have confirmed the beneficial functional effects of stem cell injection in established animal models on ED and PD. Various stem cell types have been adopted, from embryonic to adult mesenchymal cell types. Each cell type offers distinctive advantages and disadvantages. Diverse administrations of stem cells were investigated, with insignificant variability in the ultimate results. Stem cells appear to have a pronounced paracrine effect, rather than the classic engraftment and differentiation hypothesis. Phase 1 clinical trials using stem cells have not reported any severe adverse events in animals. However, these results cannot be extrapolated to draw any conclusions about efficacy in human patients. Conclusion: Stem cells have an established efficacy in preclinical studies and early clinical trials. Studies are currently being published demonstrating the safety of intrapenile injection of autologous bone marrow-and adipose tissue-derived stem cells.
European Urology, 2016
Context: Premature ejaculation (PE) is the most prevalent male sexual dysfunction. In the last fe... more Context: Premature ejaculation (PE) is the most prevalent male sexual dysfunction. In the last few years, several pharmacologic approaches for oral or topical treatment of PE have been studied. Objective: To systematically review the literature on the outcome of pharmacologic interventions for PE on intravaginal ejaculation latency time (IELT) in comparison to placebo. Evidence acquisition: A systematic literature search of PubMed and Scopus using the term ''premature ejaculation'' was performed on 10 April 2015. Full-text articles on prospective randomized controlled trials (RCTs) investigating pharmacotherapy were included. The main outcome measure was IELT. Evidence synthesis: Out of 266 unique records, a total of 22 were reviewed. The majority of RCTs were of unclear methodological quality because of limited reporting of methods. Pooled evidence suggests that selective serotonin reuptake inhibitors (SSRIs), topical anesthetic creams (TAs), tramadol, and phosphodiesterase type 5 inhibitors (PDE5is) are more effective than placebo at increasing IELT (all p < 0.05). However, interpretation of the current meta-analyses may be impaired as a result of frequent heterogeneity in the pooled analyses (all I 2 > 70%). Only pooled analyses for dapoxetine 30 mg and 60 mg were characterized by homogeneous data (both I 2 < 30%) while showing a modest but statistically significant improvement in IELT compared with placebo (mean difference 1.39 min, 95% confidence interval 1.23-1.54 min; p < 0.00001). Conclusions: Meta-analysis revealed that treatment with dapoxetine significantly improves IELT in patients with PE but with modest efficacy. The efficacy of SSRIs, TAs, tramadol, and PDE5is remains unclear owing to high heterogeneity of the available RCT data. There is a persisting need for drug research and development in the field. Patient summary: Premature ejaculation is a condition for which the cause is not well understood. Several types of treatment with medium to low efficacy are available. More research is necessary to identify the ideal treatment.
The Journal of pharmacology and experimental therapeutics, Jan 6, 2015
The transient receptor potential (TRP) melastin 8 ion channel (TRPM8) is implicated in bladder se... more The transient receptor potential (TRP) melastin 8 ion channel (TRPM8) is implicated in bladder sensing but limited information on TRPM8 antagonists in bladder overactivity (BO) is available. This study characterizes a new TRPM8-selective antagonist (DFL23448) and evaluates it in cold-induced behavioral tests and on bladder function and experimental BO in vivo in rats. DFL23448 displayed IC50 values of 10 and 21nM in hTRPM8 HEK-293 cells activated by Cooling Agent 10 or cold, but had limited activity (IC50 > 10μM) at TRPV1, TRPA1, TRPV4, or at various G-protein-coupled receptors. In rats, DFL23448 had a half-life of 37 minutes (intravenous; i.v.) or 4.9 hours (oral). DLF23448 (10mg/kg, i.v) reduced icilin-induced wet-dog shakes in rats. Intravesical (i.ves.) DFL23448 (10mg/L) but not vehicle increased micturition intervals (MI), micturition volumes (MV) and bladder capacity (BC). During BO by i.ves. PGE2, vehicle controls exhibited reductions of MI, MV and BC by 37-39%, whereas th...
Nature reviews. Urology, Jan 14, 2015
The description of the nerve-sparing technique of radical prostatectomy by Walsh was one of the m... more The description of the nerve-sparing technique of radical prostatectomy by Walsh was one of the major breakthroughs in the surgical treatment of prostate cancer in the 20(th) century. However, despite this advance and consequent technological refinements to nerve-sparing surgery, a large proportion of men still suffer from erectile dysfunction (ED) as a complication of prostatectomy. A plethora of therapeutic approaches have been proposed to optimize erectile function recovery in these patients. Several preclinical and translational studies have shown benefits of therapies including PDE5 inhibitor (PDE5I) treatment, immunomodulation, neurotrophic factor administration, and regenerative techniques, such as stem cell therapy, in animal models. However, most of these approaches have either failed to translate to clinical use or have yet to be studied in human subjects. Penile rehabilitation with PDE5Is is currently the most commonly used clinical strategy, in spite of the absence of so...
The journal of sexual medicine, 2014
Erectile dysfunction (ED) remains a frequent complication of radical prostatectomy due to injury ... more Erectile dysfunction (ED) remains a frequent complication of radical prostatectomy due to injury to the cavernous nerves (CNs). A recent microarray showed the neuropeptide galanin to be one of the most strikingly upregulated genes in the rat major pelvic ganglion (MPG) after bilateral CN crush injury (BCNI). The aim of this study is to evaluate the temporal regulation of galanin in the MPG after BCNI and its relationship to functional nerve regeneration. Changes in galanin, galanin receptor (galR), and c-JUN mRNA expression were assessed in Sprague-Dawley rats after sham operation (n = 10) and at 48 hours (n = 10), 7 (n = 10), 14 (n = 5), 21 (n = 5), 30 (n = 5), and 60 (n = 5) days after BCNI using quantitative PCR. Erectile function was assessed by measuring intracavernous pressure (ICP) divided by mean arterial pressure (MAP) during CN electrostimulation. Immunohistochemistry was performed on the MPG in sham-operated animals and 5 days after BCNI. ICP/MAP upon CN stimulation; gala...
Korean Journal of Urology, 2011
Benign prostatic hyperplasia (BPH) is highly prevalent in older men and causes substantial advers... more Benign prostatic hyperplasia (BPH) is highly prevalent in older men and causes substantial adverse effects on health. The pathogenesis of this disease is not totally clear. Recent reports have suggested a possible relationship between metabolic syndrome (MetS) and BPH. Single components of MetS (obesity, dyslipidemia, hypertension, and insulin resistance) as well as the syndrome itself may predispose patients to a higher risk of BPH and lower urinary tract symptoms (LUTS). This may stem from changes in insulin resistance, increased autonomic activity, impaired nitrergic innervation, increased Rho kinase activity, pro-inflammatory status, and changes in sex hormones that occur in association with MetS. However, the exact underlying mechanisms that regulate the potential relationship between MetS and BPH/LUTS still need to be clarified. Increased physical activity and dietary strategies may help in decreasing the incidence of MetS and its impact on BPH/LUTS. However, differences in the definitions used to address the examined predictors and endpoints preclude the possibility of arriving at definitive conclusions.
The Journal of Urology, 2011
INTRODUCTION AND OBJECTIVES: Cavernosal smooth muscle relaxation plays a major role in erectile f... more INTRODUCTION AND OBJECTIVES: Cavernosal smooth muscle relaxation plays a major role in erectile function, which is regulated by the Rho-Kinase signaling pathway and NO/cGMP pathways. Therefore we investigated the effect of ethanol intake on Rho kinase signal pathway in corpus cavernosum of type 2 DM rat. METHODS: Otsuka Long Evans Tokushima Fatty (OLETF) rats (nϭ28) and Long Evans Tokushima Otsuka (LETO, nϭ28) rats were used. LETO is a normal control of OLETF. The animals were assigned to 4 groups: LC group, LETO rats were fed with isocaloric diets (nϭ14); LE group, LETO rats were fed with 36 % ethanol, 7g/kg/day for 10 weeks (nϭ14); OC group, OLETF rats were fed with isocaloric diets (nϭ14); OE group, OLETF rats were fed with 36 % ethanol, 7g/kg/day for 10 weeks (nϭ14). During the experiment, body weights and fasting glucose levels were check in all animals. After 10 weeks, RT-PCR for 3 RhoGEFs (PDZ-RhoGEF, LARG, p115-RhoGEF) and western blot for RhoA, Rho Kinase-¥á , Rho Kinase-¥â were performed in corpus cavernosum. The expression of endothelial NO synthase (eNOS) and nervous NO synthase (nNOS) in corpus cavernosum were evaluated by immunohistochemistry. RESULTS: In non-alcoholic group, RhoGEFs (PDZ-RhoGEF, LARG, p115-RhoGEF) gene and RhoA/Rho-kinase protein expression in OLETF rats were significantly increased compared to LETO rats (P Ͻ0.05). After alcohol oral administration, the increased RhoGEFs/ RhoA/Rho-Kinase expression in OLETF rats was obviously decreased (P Ͻ0.05). The expression of eNOS and nNOS in corpus cavernosum of alcoholic group were higher than non-alcoholic group. The expression of eNOS and nNOS were decreased in OC group compared with LC, LE and OE groups. CONCLUSIONS: This study suggested oral administration of ethanol down-regulated Rho-Kinase signal pathway in corpus cavernosum of type 2 DM rat. These results showed that ethanol intake may have positive effect on erectile function in DM rat through Rho kinase pathway.
The Journal of Urology, 2014
The Journal of Urology, 2014
The Journal of Urology, 2013
fold) and 12 (11.9 fold), and had no significant effects on the expression of EP1 receptors, and ... more fold) and 12 (11.9 fold), and had no significant effects on the expression of EP1 receptors, and urine PGE2 (large variability). CONCLUSIONS: DM induced hyposensitive bladder and increased inflammatory reaction, apoptosis, expression of EP receptors, and urine NGF, but decreased bladder NGF. Targeting at NGF and EP receptors may be considered for the treatment or prevention of DM hyposensitive bladder.
The Journal of Urology, 2013
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Papers by Fabio Castiglione