Serenoa repens and its effects on male sexual function. A systematic review and meta-analysis of clinical trials

Background: Serenoa repens (SR) is a plant used to treat benign prostatic hyperplasia and prostatitis. We know that SR act as a 5\u3b1-reductase inhibitor, moreover, several studies have proved that SR has anti-inflammatory and antioxidant properties. There is some belief among patients that SR may negatively impact male sexual function. Such belief is circulating in non-medical social networks and is perhaps maintained by patients as a result of incorrect web surfing. However, it is also possible that SR may exert a "nocebo" effect thus negatively impacting on the general well-being of patients. Objective: The aim of this study is to investigate whether SR is causing negative effects on male sexual function. Methods: To ascertain the effect of SR on male sexual function, we conducted a systematic review and meta-analysis, by performing an electronic database search in accordance with the PRISMA guidelines. Results: Out of 20 included papers, 8 papers reported comparisons of SR with placebo, and 7 studies reported comparisons of SR with tamsulosin. The standardized mean difference of changes from baseline scores of sexual function was not significantly different between SR and placebo (SMD: 0.43, 95% CI: 0.18 to 1.05; I^2 = 95%). Similarly, no significant mean differences in the Male Sexual Function-4 (MSF-4) test scores were found between SR and tamsulosin (SMD: -0.31, 95% CI: -0.82 to 0.19; I^2 = 90%). Conclusions: We found no statistically significant differences between negative effects on sexual function in patients treated with SR compared to patients who received placebo. The results of our meta-analysis are similar to those of other systematic reviews. Studies are warranted to ascertain whether any such effects might occur as a result of a nocebo effect

Calcification in Peyronie's disease: Its role and clinical influence on the various symptoms and signs of the disease, including psychological impact. Our study of 551 patients

Background: The aim of study was to evaluate the impact of plaque calcification on symptoms of patients with Peyronie’s disease (PD) and to evaluate mental health in PD patients with or without calcification. Methods: We performed a retrospective analysis of the clinical database of a single andrology clinic. We extracted 551 PD patients, and we sorted them into two groups: the first group included 201 PD patients with plaque calcification; the second group included 350 PD patients without plaque calcification. The inclusion criteria for both groups were as follows: aged between 21 and 81 years; thorough and available data on clinical history; baseline levels of blood glucose, glycosylated hemoglobin, cholesterol, and triglycerides; photographic documentation of the penile curvature; dynamic penile eco-color Doppler ultrasound with plaque measurements and volume calculation; and completion of the generalized anxiety disorder—7 questionnaire, patient health questionnaire—9 (for depression), visual analog scale for penile pain measurements, and the International Index of Erectile Function (IIEF) questionnaire. Results: Plaque calcification was present in 36.4% of cases. The presence of calcification affects the presence and severity of penile curvature. Calcification is associated with the presence of hypertension. In PD patients, the prevalence of significant anxiety and significant depression was 89.1% and 57.3%, respectively. Calcification is associated with the presence of anxiety and depression but does not lead to an increase in their prevalence. Conclusions: In PD patients, the calcification was present in more than one third of cases. The size of the plaque calcification was < 15 mm in most cases. Calcification influences the presence of the curve and influences its severity. There was a prominent prevalence of anxiety and depression in PD patients

Chronic prostatitis as possible risk factor for Peyronie's disease: Psychological, sexual and prostatitis-like symptoms in patients with PD

Objective: This study aims to investigate a possible relationship between chronic prostatitis (CP) and Peyronie's disease (PD) and to characterize the psychological profile of patients suffering from PD, with or without concomitant CP. Methods: We included 539 patients with PD, of which 200 were found to have underlying CP. As a comparator population, we selected 2201 patients without PD, referring to our tertiary care clinic. In this population, we detected 384 subjects with CP. All 539 PD patients underwent photographic documentation of the penile deformation, and dynamic penile eco-color Doppler with plaque and volume measurements and answered the following questionnaires: the Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, the Visual Analog Scale for penile pain measurements, the International Index of Erectile Function (IIEF), and the NIH-Chronic Prostatitis Symptom Index. Results: The overall prevalence of chronic prostatitis in PD patients was 37.1% compared to a prevalence of 17.4% in the non-PD control population (OR = 2.79 and p < 0.0001). The severity of CP symptom total scores (NIH-CPSI) correlated significantly with the severity of erectile dysfunction (p < 0.0001). Significant anxiety was present in 89.2% of PD patients and it is more prevalent in PD patients with CP than in PD patients without CP (93.0% vs. 87.0%, respectively; p = 0.0434). Significant depression was detected in 57.1% of PD patients and it is more prevalent in PD patients with CP than in PD patients without CP (64.0% vs. 53.09%, respectively; p = 0.0173). Conclusion: Chronic prostatitis (CP) and Peyronie's disease (PD) are frequently associated. Our results demonstrate the strong impact of chronic prostatitis on the mental status of PD patients. Anxiety and depression were significantly more pronounced in PD patients with CP than in PD patients without CP

Benign prostatic obstruction (BPO) as a possible risk factor for Peyronie's disease (PD). The influence of BPO and PD on mental health

To the Editor, Our study aimed to investigate a possible relationship between benign prostatic obstruction (BPO) and Peyronie's disease (PD) and to characterize the psychological profile of patients affected by Peyronie's disease, with or without concomitant BPO. In this study, we have investigated whether there is a relationship between the two diseases. The typical symptoms of PD are as follows: penile deformation, local pain, erectile dysfunction (ED), and anxious depressive state. Benign prostatic hyperplasia (BPH) causes symptoms only in the case of urinary obstruction (benign prostatic obstruction/BPO). BPO is an emotionally stressful condition, but any type of treatment, such as surgery, by significantly decreasing LUTS, can significantly improve the general well-being of the affected patient (1). We performed a retrospective analysis of the clinical database of a single uro-andrology clinic. From the database, we considered two separate cohorts of patients observed between January 2013 and February 2023. The first cohort included 539 patients diagnosed with Peyronie's disease. As a comparator population, we considered a cohort of 2208 outpatients referred to our clinic for any disease, but not Peyronie's disease. [...

Future Needs in Mast Cell Biology.

The pathophysiological roles of mast cells are still not fully understood, over 140 years since their description by Paul Ehrlich in 1878. Initial studies have attempted to identify distinct "subpopulations" of mast cells based on a relatively small number of biochemical characteristics. More recently, "subtypes" of mast cells have been described based on the analysis of transcriptomes of anatomically distinct mouse mast cell populations. Although mast cells can potently alter homeostasis, in certain circumstances, these cells can also contribute to the restoration of homeostasis. Both solid and hematologic tumors are associated with the accumulation of peritumoral and/or intratumoral mast cells, suggesting that these cells can help to promote and/or limit tumorigenesis. We suggest that at least two major subsets of mast cells, MC1 (meaning anti-tumorigenic) and MC2 (meaning pro-tumorigenic), and/or different mast cell mediators derived from otherwise similar cells, could play distinct or even opposite roles in tumorigenesis. Mast cells are also strategically located in the human myocardium, in atherosclerotic plaques, in close proximity to nerves and in the aortic valve. Recent studies have revealed evidence that cardiac mast cells can participate both in physiological and pathological processes in the heart. It seems likely that different subsets of mast cells, like those of cardiac macrophages, can exert distinct, even opposite, effects in different pathophysiological processes in the heart. In this chapter, we have commented on possible future needs of the ongoing efforts to identify the diverse functions of mast cells in health and disease

Buccal mucosa is a promising graft in Peyronie's disease surgery. Our experience and a brief literature review on autologous grafting materials.

Aim: Peyronie's Disease (PD) is an under reported acquired benign condition that, at the moment, is not curable with medical therapy. Surgery represent the gold standard of treatment. Surgical approaches are several and they consist in "plication techniques" or plaque incision/excision with grafting of resulting albuginea defect. Among grafting procedures, albuginea defect substitution with autologous materials demonstrated over the years not inferior results respect to heterologous grafts. Buccal mucosa graft (BMG) is not usually emphasized in many review articles and clinical series are yet limited. Methods: We present our experience with seventeen plaque incision procedures and BMG in surgical correction of complex penile curvatures due to PD performed in a period of 30 months. Our analyses was focused on buccal mucosa graft characteristics as major determinant of the surgical success. We also conducted a brief literature review on autologous grafting materials used in reconstructive penile surgery for PD. Results: Our cosmetics and functional results consists in a 100% of functional penile straightening with no relapses and 5,8% of de novo erectile dysfunction. Mean age was 56.4 years, mean follow-up of 22.5 (6-36) months. No complications graft related were observed. Operative time was 115.3 minutes in mean. Over 94% of patients referred they were "really much better" and "much better" satisfied based on PGI-I questionnaire administrated at the last follow- up visit. Conclusion: BMG is revealing as an optimal choice for reconstructive surgery in PD. Anatomical characteristics consisting in the great elasticity, the quick integration time and the easy harvesting technique lead to high cosmetics and functional success rate, without omitting economical and invasiveness aspects

Urokinase Induces Basophil Chemotaxis through a Urokinase Receptor Epitope That Is an Endogenous Ligand for Formyl Peptide Receptor-Like 1 and -Like 2

AbstractBasophils circulate in the blood and are able to migrate into tissues at sites of inflammation. Urokinase plasminogen activator (uPA) binds a specific high affinity surface receptor (uPAR). The uPA-uPAR system is crucial for cell adhesion and migration, and tissue repair. We have investigated the presence and function of the uPA-uPAR system in human basophils. The expression of uPAR was found at both mRNA and protein levels. The receptor was expressed on the cell surface of basophils, in the intact and cleaved forms. Basophils did not express uPA at either the protein or mRNA level. uPA (10−12–10−9 M) and its uPAR-binding N-terminal fragment (ATF) were potent chemoattractants for basophils, but did not induce histamine or cytokine release. Inactivation of uPA enzymatic activity by di-isopropyl fluorophosphate did not affect its chemotactic activity. A polyclonal Ab against uPAR inhibited uPA-dependent basophil chemotaxis. The uPAR-derived peptide 84–95 (uPAR84–95) induced basophil chemotaxis. Basophils expressed mRNA for the formyl peptide receptors formyl peptide receptor (FPR), FPR-like 1 (FPRL1), and FPRL2. The FPR antagonist cyclosporin H prevented chemotaxis induced by FMLP, but not that induced by uPA and uPAR84–95. Incubation of basophils with low and high concentrations of FMLP, which desensitize FPR and FPRL1, respectively, but not FPRL2, slightly reduced the chemotactic response to uPA and uPAR84–95. In contrast, desensitization with WKYMVm, which also binds FPRL2, markedly inhibited the response to both molecules. Thus, uPA is a potent chemoattractant for basophils that seems to act through exposure of the chemotactic uPAR epitope uPAR84–95, which is an endogenous ligand for FPRL2 and FPRL1

Urologists' knowledge base and practice patterns in Peyronie's disease. A national survey of members of the italian andrology society.

Peyronie's disease is a chronic inflammatory disease involving the formation of plaque in the tunica albuginea of the corpora cavernosa, resulting in penis deformity. It is often associated with penile pain, especially in younger patients, but it is not rare for pain to be absent; the disease is also associated with erectile dysfunction and a depressive state in a large percentage of cases. Objective: Aim of our study was to explore the basic knowledge base and diagnostic and therapeutic practice patterns in Peyronie's disease (PD) of a large number of physicians belonging to the Italian Andrology Society (SIA). Methods: Our survey is based on two questionnaires which were e-mailed to the members of the SIA. The first questionnaire explored diagnostic and therapeutic practice patterns of SIA physicians, while the second questionnaire focused on their knowledge of the disease, as well as their training and level of experience in the specific field. We then planned to compare our outcomes with similar PD surveys from other countries. Results: The first questionnaire was answered by 142 SIA physicians. The second questionnaire was answered by 83 SIA physicians. Most respondents (74.6%) chose penile ultrasonography as first-line diagnostic approach and 47.1% prefer to perform a color Doppler ultrasound after pharmaco-induced erection. Concerning the therapeutic practice patterns in active stage of the disease, most respondents (99.29%) prefer conservative medical therapy. Additionally, most respondents (64.78%), when failure of conservative treatment had been established, considered surgical treatment necessary, specifically corporoplasty, which may be associated with other techniques. Conclusions: The results of our survey show that, in comparison to their foreign counterparts, Italian SIA uro-andrologists have a more proactive diagnostic approach right from when patients first present. When PD is still in its active stage, SIA uro-andrologists mostly opt for medical therapy. In advanced disease or if conservative treatment fails, our survey indicates a greater preference for surgical treatment. Answers to the theoretical knowledge questions showed that SIA physicians have a good understanding of the disease's etiology, epidemiology, and clinical picture, and of the appropriate indications for treatment

Expression and Functions of the Vascular Endothelial Growth Factors and Their Receptors in Human Basophils

Abstract Angiogenesis is a multistep complex phenomenon critical for several inflammatory and neoplastic disorders. Basophils, normally confined to peripheral blood, can infiltrate the sites of chronic inflammation. In an attempt to obtain insights into the mechanism(s) underlying human basophil chemotaxis and its role in inflammation, we have characterized the expression and function of vascular endothelial growth factors (VEGFs) and their receptors in these cells. Basophils express mRNA for three isoforms of VEGF-A (121, 165, and 189) and two isoforms of VEGF-B (167 and 186). Peripheral blood and basophils in nasal polyps contain VEGF-A localized in secretory granules. The concentration of VEGF-A in basophils was 144.4 ± 10.8 pg/106 cells. Immunologic activation of basophils induced the release of VEGF-A. VEGF-A (10–500 ng/ml) induced basophil chemotaxis. Supernatants of activated basophils induced an angiogenic response in the chick embryo chorioallantoic membrane that was inhibited by an anti-VEGF-A Ab. The tyrosine kinase VEGFR-2 (VEGFR-2/KDR) mRNA was expressed in basophils. These cells also expressed mRNA for the soluble form of VEGFR-1 and neuropilin (NRP)1 and NRP2. Flow cytometric analysis indicated that basophils express epitopes recognized by mAbs against the extracellular domains of VEGFR-2, NRP1, and NRP2. Our data suggest that basophils could play a role in angiogenesis and inflammation through the expression of several forms of VEGF and their receptors

Congenital penile curvature as a possible risk factor for the onset of Peyronie's disease, and psychological consequences of penile curvature

Objective: To investigate a possible relationship between a history of congenital penile curvature (CPC) and Peyronie's disease (PD), and to characterize the psychological profile of patients suffering from PD, with or without concomitant CPC. Methods: We included 519 patients with Peyronie's disease (PD), of which 73 were found to have underlaying CPC. As a comparator population, we selected 2166 patients without PD, referring to our tertiary care clinic. In this population we detected 15 subjects with CPC. All patients completed the GAD-7 (Generalized-Anxiety-Disorder - 7 questions) and the PHQ-9 (Patient-Health-Questionnaire - 9 questions) questionnaires. Results: The overall prevalence of CPC in PD-patients was 14.07%, compared to a prevalence of 0.69% in the non-PD control population (p &lt; 0.00001). Moderate-to-severe anxiety was found to be present in 89.4% of all PD-patients. Significantly higher proportions of patients with CPC associated with PD showed severe anxiety, compared to patients with PD alone (57.5% vs. 36.7%, respectively, p = 0.0008). Moderate- severe depression was found to be present in 57.8% of all PD- patients. Significantly higher proportions of PD patients with a history of CPC showed severe depression, compared to patients with PD alone (13.6% vs. 3.36%, respectively, p &lt; 0.0002). GAD-7 median scores were significantly higher in patients with more severe penile curvatures (&gt; 45°; p = 0.029). We did not detect a statistically significant difference between PHQ-9 medi- an scores based on the severity of PD (p = 0.53). Analysis of PHQ-9 and GAD-7 median scores showed significantly worse depressive and anxious symptoms in younger patients (p &lt; 0.001 and p = 0.0013, respectively). Conclusions: The presence of congenital-penile-curvature may represent a risk factor for the subsequent onset of Peyronie's disease. Moderate/severe anxiety and moderate/severe depression were reported in a high fraction of cases. Anxiety was significantly higher in patients with more severe penile-curvatures, and depression was present independently of the degree of penile curvature. Depression and anxiety were found to be more severe in younger subjects