Low intensity extracorporeal shockwave therapy for erectile dysfunction: a study in an Indian population.

INTRODUCTION: Erectile dysfunction (ED) has been shown to be associated with a number of physical conditions and affects not only physical but also psychosocial health. Currently oral, on-demand phosphodiesterase type 5 inhibitors (PDE5i) are preferred first line treatment. Though effective, these drugs have limitations and are associated with significant non-compliance, side effects and do not reverse the underlying pathology. Non-invasive low intensity shockwave therapy (LISWT) has been shown to significantly improve erectile function in men previously PDE5i dependent. We describe our experience and results with this therapy in an Indian population of men with ED. This study assessed the efficacy of low intensity extracorporeal shockwave therapy (LI-ESWT) on Indian men with organic ED who had previously responded to PDE5i. MATERIALS AND METHODS: All the patients underwent a 1 month PDE5i washout period. Men were randomized to receive either 12 sessions of LI-ESWT (n = 95) or placebo/sham therapy (n = 40). Before the first treatment, erectile function and penile hemodynamics were assessed to substantiate a vascular etiology for the ED. Outcomes were assessed using Erection Hardness Score (EHS), International Index of Erectile Function-Erectile Function Domain (IIEF-EF domain) and Clinical Global Impression of Change (CGIC) scores at 1, 3, 6, 9 and 12 months post-treatment. RESULTS: We found a significant increase in the EHS and IIEF-EF Domain scores from visit 1 to follow up 5 (12 months) in the treated group compared to the placebo group. By 1 month after treatment there were highly significant differences between the LI-ESWT and placebo groups (p < 0.0001). Out of 60 men in the LI-ESWT group who completed the study, 47 (78%) men at FU1 and 43 (71%) at FU5 who were initially unable to achieve spontaneous erections hard enough for penetration (EHS ≤ 2) were able to do so (EHS ≥ 3) compared to none in the placebo group. The treatment was well tolerated and none of the men experienced treatment related discomfort or reported any adverse effects from the treatment. CONCLUSIONS: In this double-blind, placebo-controlled study, LI-ESWT demonstrated a positive long term clinical effect with improvement in erectile function of Indian men with vasculogenic ED who were prior responders to PDE5i therapy. The efficacy and tolerability of this treatment, coupled with its long term benefits and rehabilitative characteristics, make it an attractive new therapeutic option for men with vasculogenic erectile dysfunction.

Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction in Diabetic Patients.

INTRODUCTION: The cause of erectile dysfunction (ED) in diabetic patients is complex and involves both neurogenic and vasculogenic components and is often hard to treat. AIM: To study the effect of low-intensity extracorporeal shock wave therapy (Li-ESWT) therapy on a subgroup of diabetic patients with ED who are responders (PDE5I-R) and non-responders (PDE5I-NR) to phosphodiesterase 5 inhibitors (PDE5I). METHODS: Analysis of pooled data from 5 double-blind, sham-controlled trials was performed. In this sub-analysis, of 350 patients in the PDE5I-R group and with vasculogenic ED, we found 61 patients with diabetes mellitus who underwent LI-ESWT. Another 48 patients (of 53) belonged to the PDE5I-NR group. Baseline efficacy was evaluated with the International Index of Erectile Function-Erectile Function domain questionnaire (IIEF-EF) for the PDE5I-R and with Erection Hardness Score, IIEF-EF, and flow-mediated dilation technique for the PDE5I-NR. MAIN OUTCOME MEASURES: Change in the IIEF-EF score after treatment of diabetes-induced ED with Li-ESWT in the PDE5i-R group vs the PDE5i-NR group. RESULTS: LI-ESWT therapy was found to be effective in both subgroups of diabetic patients. Minimally clinical important difference in IIEF-EF score was achieved in 50%, 79.5%, 77.3%, and 65.9% of the subjects in the active group in after the sixth shockwave (SW) treatment evaluation (just before initiating the seventh SW session) and at 1 month, 6 months, and 12 months after the last SW treatment, respectively. The difference among the groups was significant (P < .05) after the sixth treatment and in all the follow-up periods. In the PDE5I-NR group, 55% of the active group were converted to PDE5I-5-R after LI-ESWT. The difference between the active and sham groups was statistically significant in all the tested measures (P < .001). CONCLUSION: LI-ESWT is safe and effective for the treatment of ED in PDE5I-R and PDE5I-NR groups. Spivak L, Shultz T, Appel B, et al. Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction in Diabetic Patients. Sex Med Rev 2021;9:619-627.

Beta-tubulin cofactor D and ARL2 take part in apical junctional complex disassembly and abrogate epithelial structure.

In epithelial cells, the apical junctional complex (AJC), composed of tight junctions (TJs) and adherens junctions (AJs), maintains cell-surface polarity by forming a fence that prevents lateral movement and diffusion of proteins and lipids between the apical and basolateral PM and holds the epithelial monolayer intact through cell-cell contacts. Disassembly of this complex is a prime event in development and cell transformation. Maintenance of the AJC has been shown to involve mainly the actin cytoskeleton. Recent findings also point to the involvement of the microtubule (MT) system. Here we show the first evidence that in polarized epithelial MDCK cells, ARF-like protein 2 (ARL2) and beta-tubulin cofactor D, known to be involved in MT dynamics, have a role in disassembly of the AJC followed by cell dissociation from the epithelial monolayer, which is not dependent on MT depolymerization. In addition, we show that beta-tubulin cofactor D is partially localized to the lateral PM through its 15 C-terminal amino acids and intact MTs. ARL2 inhibited beta-tubulin cofactor D-dependent cell dissociation from the monolayer and AJC disassembly. To our knowledge, this is the first evidence that beta-tubulin cofactor D plays a role in cells independent of its presumed role in folding tubulin heterodimers. We conclude that ARL2 and beta-tubulin cofactor D participate in AJC disassembly and epithelial depolarization.

The beginning of a new era: treatment of erectile dysfunction by use of physical energies as an alternative to pharmaceuticals.

This introductory manuscript aims to familiarize the concept of the ability of certain forces or energies applied on the penis. This concept is described and discussed in more detail for three optional applicative energies; shock wave energy via mechano-transduction, ultrasound energy via its theoretical unique effect on the cellular membrane, specifically cyclic separation of the two phospholipid layers, creating biochemical, functional and structural tissue changes. Radio frequency energy via its heating effect is proven to induce immediate changes on collagen strucures and on realignment of collagen fibers, as well as induction of local vasodilation. Applying any of these energies on the erectile tissue may potentially affect biochemical processes, which through different mechanisms lead to a beneficial clinical effect on erectile function.

Justice, leader-member exchange, and job performance: are their relationships mediated by organizational culture?

The hypothesis that organizational justice is linked to leader-member exchange, which in turn affects job performance, was examined. It was predicted that two dimensions of organizational culture, employee supportiveness and attention to detail, would affect both leader-member exchange and organizational justice. Results from a sample of 75 employees of a public service organization found solid support for the predicted model. Contrary to expectations, however, the two aspects of organizational culture were found to play a mediating role: they were affected by organizational justice and in turn affected leader-member exchange. The theoretical implications of the results are discussed.

EFA6 regulates endosomal trafficking and affects early endosomes in polarized MDCK cells.

The small-GTPase family of ADP ribosylation factors (ARFs) recruit coat proteins to promote vesicle budding. ARFs are activated by an association with sec7-containing exchange factors which load them with GTP. In epithelial cells, the small GTPase ARF6 operates within the endocytic system and has been shown to associate with ARNO to promote apical endocytosis and early to late endosomal trafficking. EFA6 has been shown to stimulate tight-junction formation and maintenance. Here, we show that in polarized epithelial MDCK cells, EFA6 is localized to early endosomes, causes their dramatic enlargement, and promotes basolateral targeting of IgA, which is normally targeted to the apical PM. These results suggest that the physiological function of ARF6 within the endocytic system is regulated by the exchange factor it associates with.