Assessment of the treatment effectiveness of men with mild and medium degree of erectile dysfunction.

OBJECTIVE: . Aim: To assess the effectiveness of monotherapy and complex treatment of patients with erectile dysfunction depending on its severity. PATIENTS AND METHODS: Materials and Methods: Men with moderate and mild erectile dysfunction took part in the study, who, in turn, were divided into groups, depending on the treatment, with the evaluation of the results of the International Index of Erectile Function (MIEF-15), the state of cavernous hemodynamics and the function of the vascular endothelium before and after treatment. RESULTS: Results: In patients with an average degree of severity, who received complex treatment including a course of low-energy shock wave therapy, against the background of taking sildenafil and L-arginine, the best results were obtained in the quality of erection and increased cavernous blood flow, which positively affected satisfaction with sexual intercourse and overall satisfaction. It has also been proven that the function of the endothelium was improved in patients receiving L-arginine, due to which there was a probable decrease in endothelin-1. A probable improvement of erectile function was obtained in the group of patients with a mild degree who received L-arginine, and there was no statistical difference from the indicators in the group who received sildenafil, which was confirmed by the data of dopplerography. CONCLUSION: Conclusions: Patients with an average degree of erectile dysfunction require comprehensive treatment. The use of L-arginine can be an alternative to phosphodiesterase type 5 inhibitors in the treatment of mild erectile dysfunction.

Effect of low-energy shock wave therapy on intravesical epirubicin delivery in a rat model of bladder cancer.

OBJECTIVES: To study the efficacy of low-energy shock wave therapy (LESW) on enhancing intravesical epirubicin (EPI) delivery in a rat model of bladder cancer (BCa). MATERIALS AND METHODS: A total of 100 female Fischer rats were randomly allocated into five groups: control; BCa; LESW; EPI; and EPI plus LESW. After BCa induction by N-butyl-N-(4-hydroxybutyl)nitrosamine, EPI (0.6 mg/0.3 mL of EPI diluted in 0.3 mL saline) or saline (0.6 mL) was administered and retained in the bladders for 1 h with or without LESW treatment (300 pulses at 0.12 mJ/mm2 ). This was repeated weekly for 6 weeks. Survival was then calculated, rats were weighed and their bladders were harvested for bladder/body ratio estimation, histopathological examination, p53 immunostaining, miR-210, hypoxia-inducible factor (HIF)-1α, tumour necrosis factor (TNF)-α and interleukin (IL)-6 relative gene expression and fluorescence spectrophotometric drug quantification. Heart and blood samples were also collected for assessment of the safety profile and toxicity. RESULTS: The EPI plus LESW group had significantly lower mortality rates, loss of body weight and bladder/body ratio. Histopathological results in terms of grossly visible bladder lesions, mucosal thickness, dysplasia formation and tumour invasion were significantly better in the combined treatment group. The EPI plus LESW group also had statistically significant lower expression levels of p53 , miR-210, HIF-1α, TNF-α and IL-6. LESW increased urothelial concentration of EPI by 5.7-fold (P < 0.001). No laboratory variable exceeded the reference ranges in any of the groups. There was an improvement of the indicators of EPI-induced cardiomyopathy in terms of congestion, hyalinization and microvesicular steatosis of cardiomyocytes (P = 0.068, 0.003 and 0.046, respectively) in the EPI plus LESW group. CONCLUSIONS: The combined use of intravesical EPI and LESW results in less BCa invasion and less dysplasia formation, as LESW increases urothelial permeability of EPI and enhances its delivery into tumour tissues, without subsequent toxicity.

[Low-intensity pulsed ultrasound versus low-energy shock wave in the treatment of neurogenic penile erectile dysfunction].

OBJECTIVE: To investigate the effect and safety of low-intensity pulsed ultrasound (LIPUS) versus low-energy shock wave (LESW) in the treatment of neurogenic penile ED in male SD rats. METHODS: Twenty-four 12-week-old male SD rats were randomly divided into four groups of an equal number: sham operation, bilateral cavernous nerves injury (BCNI), LIPUS (300 mW /cm2, 3 times a week for 2 weeks), and LESW (300 strokes once, 3 times a week for 2 weeks). At 28 days after intervention, the erectile function of the rats was assessed by comparing the ratio of maximum intracavernous pressure to mean arterial pressure (ICPmax/MAP), and the histopathological changes in the corpus cavernosum of the penis were observed by immunohistochemistry, immunofluorescence staining, and Masson trichromatic staining. RESULTS: After treatment, the LIPUS and LESW groups, compared with the BCNI group, showed significantly increased ICPmax/MAP ratio (0.56 ± 0.13 and 0.55 ± 0.10 versus 0.35 ± 0.14, P = 0.017 and P = 0.013), improved smooth muscle/collagen value (0.08 ± 0.01 and 0.08 ± 0.02 versus 0.06 ± 0.02, P = 0.017 and P = 0.019), and elevated proportion of smooth muscle to cavernosum (0.20 ± 0.05 and 0.21 ± 0.03 versus 0.15 ± 0.02, P = 0.046 and P = 0.020), with no statistically significant difference between the LIPUS and LESW groups. No obvious adverse reactions were observed in the LIPUS or LESW group. CONCLUSIONS: Both LIPUS and LESW can effectively improve penile erectile function and repair histopathological injury in the animal model of neurogenic ED.

Low-energy shock wave pretreatment recruit circulating endothelial progenitor cells to attenuate renal ischaemia reperfusion injury.

Low-energy shock wave (LESW) has been recognized as a promising non-invasive intervention to prevent the organs or tissues against ischaemia reperfusion injury (IRI), whereas its effect on kidney injury is rarely explored. To investigate the protective role of pretreatment with LESW on renal IRI in rats, animals were randomly divided into Sham, LESW, IRI and LESW + IRI groups. At 4, 12, 24 hours and 3 and 7 days after reperfusion, serum samples and renal tissues were harvested for performing the analysis of renal function, histopathology, immunohistochemistry, flow cytometry and Western blot, as well as enzyme-linked immunosorbent assay. Moreover, circulating endothelial progenitor cells (EPCs) were isolated, labelled with fluorescent dye and injected by tail vein. The fluorescent signals of EPCs were detected using fluorescence microscope and in vivo imaging system to track the distribution of injected circulating EPCs. Results showed that pretreatment with LESW could significantly reduce kidney injury biomarkers, tubular damage, and cell apoptosis, and promote cell proliferation and vascularization in IRI kidneys. The renoprotective role of LESW pretreatment would be attributed to the remarkably increased EPCs in the treated kidneys, part of which were recruited from circulation through SDF-1/CXCR7 pathway. In conclusion, pretreatment with LESW could increase the recruitment of circulating EPCs to attenuate and repair renal IRI.

Low energy shock wave-delivered intravesical botulinum neurotoxin-A potentiates antioxidant genes and inhibits proinflammatory cytokines in rat model of overactive bladder.

PURPOSE: To study the effect of intravesical instillation of botulinum neurotoxin-A (BoNT-A) combined with low energy shock wave (LESW) for treatment of overactive bladder (OAB) in a rat model and to investigate its effect on the associated inflammatory and oxidative stress process. MATERIAL AND METHODS: Forty rats were subdivided into four equal groups: normal control group, OAB group, LESW group, and BoNT-A plus LESW group. Cystometrogram (CMG) changes and histopathological changes in the bladder mucosa were assessed in the different groups. Oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]) and proinflammatory cytokines (tumor necrotic factor-α [TNF-α] and interleukin-6 [IL-6]) were compared among groups. RESULTS: BoNT-A plus LESW group showed statistically significant lower amplitude (p = .001) and lower frequency of detrusor contractions (p = .01) compared to LESW, which showed no statistically significant difference in comparison to the OAB group. Also, the combined group significantly reduced submucosal edema and inflammatory cell infiltrate scores compared to all groups (p < .05). LESW was associated with 42% reduction of MDA expression while, LESW plus BoNT-A decreased it by 68% (p < .001). Also, LESW and LESW plus BoNT-A increased SOD expression by 43% and 75%, respectively (p < .001). LESW plus BoNT-A was associated with statistically significant lower expression of TNF-α and IL-6 expression by 37% and 66% in comparison to LESW group (p = .001). CONCLUSION: Intravesical instillation of BoNT-A plus LESW is an effective method for increasing the urothelial permeability to BoNT-A and enhancing its therapeutic effect against OAB in rat model through the expression of a substantial anti-inflammatory and antioxidative stress effect.

Extracorporeal shock wave therapy decreases COX-2 by inhibiting TLR4-NFκB pathway in a prostatitis rat model.

BACKGROUND: This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism. METHODS: RWPE-2 cells were randomly divided into three groups: (a) RWPE-2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE-2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague-Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 ß-estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA. RESULTS: ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX-2) through inhibiting TLR4-NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2-COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate. CONCLUSIONS: ESWT improved CP/CPPS and reduced inflammation by degrading COX-2 in microenvironment through TLR4-NFκB-inhibiting pathway. TRAF2 regulator in ERK1/2-COX-2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.

Effect of extracorporeal low-energy shock wave on diabetic gastroparesis in a rat model.

BACKGROUND AND AIM: Delayed gastric emptying occurs in more than 50% of chronic diabetic patients, and this is associated with significant impairments in quality of life. Traditional therapy for delayed gastric emptying has focused on supportive treatment, and there is no significant effective therapy. The effect of low-energy shock wave on gastric motility is never studied. We investigated low-energy shock wave on gastric motility in a diabetic rat model. METHODS: Twenty-eight male Wistar rats were studied and separated in three groups in randomized order as control, diabetic rats received shock wave, and diabetic rats received the sham procedure. Antral area and motility were recorded using the transabdominal ultrasound. Blood was taken for measurement of gastric motility peptides. Subjects were killed for immunohistochemical stain analysis of enteric plexus of the stomach. RESULTS: We successfully induced 20 diabetic rats and set ultrasound for measuring rat gastric contract and emptying model and demonstrated that 6 weeks of low-energy shock wave could promote gastric contraction and emptying in diabetic rats. Moreover, we demonstrated that shock wave could increase defecation and feces and decrease serum cholesterol and triglycerol. However, no effect on glycohemoglobin and gastric motility peptides was recorded. In the immunohistochemical staining, shock wave increased expression of gastric myenteric neuron plexus. CONCLUSION: Low-energy shock wave can increase gastric contraction and emptying by activating axonal regeneration and increasing myenteric plexus, but not related with motility peptides.

Defocused low-energy shock wave activates adipose tissue-derived stem cells in vitro via multiple signaling pathways.

BACKGROUND AIMS: We found defocused low-energy shock wave (DLSW) could be applied in regenerative medicine by activating mesenchymal stromal cells. However, the possible signaling pathways that participated in this process remain unknown. In the present study, DLSW was applied in cultured rat adipose tissue-derived stem cells (ADSCs) to explore its effect on ADSCs and the activated signaling pathways. METHODS: After treating with DLSW, the cellular morphology and cytoskeleton of ADSCs were observed. The secretions of ADSCs were detected. The expressions of ADSC surface antigens were analyzed using flow cytometry. The expressions of proliferating cell nuclear antigen and Ki67 were analyzed using western blot. The expression of CXCR2 and the migrations of ADSCs in vitro and in vivo were detected. The phosphorylation of selected signaling pathways with or without inhibitors was also detected. RESULTS: DLSW did not change the morphology and phenotype of ADSCs, and could promote the secretion, proliferation and migration of ADSCs. The phosphorylation levels were significantly higher in mitogen-activated protein kinases (MAPK) pathway, phosphoinositide 3-kinase (PI-3K)/AKT pathway and nuclear factor-kappa B (NF-κB) signaling pathway but not in Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Furthermore, ADSCs were not activated by DLSW after adding the inhibitors of these pathways simultaneously. CONCLUSIONS: Our results demonstrated for the first time that DLSW could activate ADSCs through MAPK, PI-3K/AKT and NF-κB signaling pathways. Combination of DLSW and agonists targeting these pathways might improve the efficacy of ADSCs in regenerative medicine in the future.

Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in a Pelvic Neurovascular Injuries Rat Model.

INTRODUCTION: Erectile dysfunction (ED) caused by pelvic injuries is a common complication of civil and battlefield trauma with multiple neurovascular factors involved, and no effective therapeutic approach is available. AIMS: To test the effect and mechanisms of low-energy shock wave (LESW) therapy in a rat ED model induced by pelvic neurovascular injuries. METHODS: Thirty-two male Sprague-Dawley rats injected with 5-ethynyl-2'-deoxyuridine (EdU) at newborn were divided into 4 groups: sham surgery (Sham), pelvic neurovascular injury by bilateral cavernous nerve injury and internal pudendal bundle injury (PVNI), PVNI treated with LESW at low energy (Low), and PVNI treated with LESW at high energy (High). After LESW treatment, rats underwent erectile function measurement and the tissues were harvested for histologic and molecular study. To examine the effect of LESW on Schwann cells, in vitro studies were conducted. MAIN OUTCOME MEASUREMENTS: The intracavernous pressure (ICP) measurement, histological examination, and Western blot (WB) were conducted. Cell cycle, Schwann cell activation-related markers were examined in in vitro experiments. RESULTS: LESW treatment improves erectile function in a rat model of pelvic neurovascular injury by leading to angiogenesis, tissue restoration, and nerve generation with more endogenous EdU(+) progenitor cells recruited to the damaged area and activation of Schwann cells. LESW facilitates more complete re-innervation of penile tissue with regeneration of neuronal nitric oxide synthase (nNOS)-positive nerves from the MPG to the penis. In vitro experiments demonstrated that LESW has a direct effect on Schwann cell proliferation. Schwann cell activation-related markers including p-Erk1/2 and p75 were upregulated after LESW treatment. CONCLUSION: LESW-induced endogenous progenitor cell recruitment and Schwann cell activation coincides with angiogenesis, tissue, and nerve generation in a rat model of pelvic neurovascular injuries.

Activation of bone marrow-derived mesenchymal stromal cells-a new mechanism of defocused low-energy shock wave in regenerative medicine.

BACKGROUND AIMS: Defocused low-energy shock wave (DLSW) therapy has shown effectiveness in regenerative medicine. The mechanism of action was mainly focused on the pathophysiological improvement at the wound tissues. In this study, the activation of stem cells treated by DLSW was first examined as an important pathway during the healing process. METHODS: Cultured rat bone marrow-derived mesenchymal stromal cells (BMSC) were treated by DLSW before each passage. The untreated BMSC served as a control. The secretions of vascular endothelial growth factor (VEGF) and CXC ligand 5 (CXCL5) were tested by means of enzyme-linked immunoassay. Flow cytometry was performed to analyze the BMSC (passage 4) surface antigen expressions (CD166, CD44 and CD34). The expressions of proliferating cell nuclear antigen and Ki67 were analyzed by means of Western blot. The healing abilities of conditioned media of shocked and unshocked BMSC were examined by Matrigel-based capillary-like tube formation assay and rat major pelvic ganglia culture test. RESULTS: The shocked BMSC secreted more VEGF and CXCL5 than did those of unshocked BMSC. The expressions of CD166, CD44 and CD34 showed no significant differences (P > 0.05) between the shocked and unshocked BMSC. The shocked BMSC demonstrated higher expressions of proliferating cell nuclear antigen (P < 0.01) and Ki67 (P < 0.01) than did those of unshocked BMSC. The shocked BMSC conditioned medium showed higher ability to enhance the growth of major pelvic ganglia neurites (P < 0.05) and Matrigel-based endothelial tube-like formation (P < 0.05). CONCLUSIONS: DLSW did not interfere with the expressions of cell surface markers. DLSW enhanced the secretion and proliferation of BMSC and promoted angiogenesis and nerve regeneration in vitro.

Low-Energy Shock Wave Plus Intravesical Instillation of Botulinum Toxin A for Interstitial Cystitis/Bladder Pain Syndrome: Pathophysiology and Preliminary Result of a Novel Minimally Invasive Treatment.

Low-energy shock wave (LESW) therapy is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment has been demonstrated to be effective in treating chronic prostatitis and pelvic pain syndrome as well as overactive bladder, and it has a potential effect on interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. LESW reduces pain behavior, downregulates nerve growth factor expression, and suppresses bladder overactivity by decreasing the expression of inflammatory proteins. Previous rat IC models have shown that LESW can increase urothelial permeability, facilitate intravesical delivery of botulinum toxin A (BoNT-A), and block acetic acid-induced hyperactive bladder, suggesting that LESW might be a potential therapeutic module for relieving bladder inflammatory conditions, such as bladder oversensitivity, IC/BPS, and overactive bladder. A recent clinical trial showed that LESW monotherapy was associated with a significant reduction in pain scores and IC symptoms. BoNT-A detrusor injection or liposome-encapsulated BoNT-A instillation could also inhibit inflammation and improve IC symptoms. However, BoNT-A injection requires anesthesia and certain complications might occur. Our preliminary study using LESW plus intravesical BoNT-A instillation every week demonstrated an improvement in global response assessment without any adverse events. Moreover, an immunohistochemistry study revealed the presence of cleaved SNAP25 protein in the suburothelium of IC bladder tissue, indicating that BoNT-A could penetrate across the urothelial barrier after application of LESW. These results provide evidence for the efficacy and safety of this novel IC/BPS treatment by LESW plus BoNT-A instillation, without anesthesia, and no bladder injection. This article reviews the current evidence on LESW and LESW plus intravesical therapeutic agents on bladder disorders and the pathophysiology and pharmacological mechanism of this novel, minimally invasive treatment model for IC/BPS.

Efficacy of low energy shock-wave therapy generated using an electrohydraulic device in the treatment of ED: A systematic review and meta-analysis of randomized controlled trials. / Eficacia de el tratamiento con ondas de choque de baja energía utilizando un aparato electrohidráulico en el tratamiento de la difunción eréctil: revisión sistemática y metanálisis de ensayos randomizados.

OBJECTIVES: Over 50% of elderly men and 70% of male cardiac patients suffer from erectile dysfunction (ED). Although pharmacotherapy is effective and safe, it only brings a short-term improvement and may cause side effects. Low energy shock-wave therapy (LESWT) is a promising causative modality for the treatment of ED. The evidence is still limited with different results obtained using different devices. The aim of this work was to evaluate evidence from randomized controlled trials regarding the efficacy of LESWT generated by an electrohydraulic unit for the treatment of ED. METHODS: A systematic review of the literature was conducted in PubMed on May 20th, 2018 and supplemented by a Google search of grey literature, as well as a hand search of the bibliographies of retrieved articles. Out of 34 studies, 5 studies on 354 patients were included in the quantitative synthesis. RESULTS: The studies evaluated an abridged International Index of Erectile Function (IIEF-5), the Erectile Hardness Scale (EHS) and Flow-Mediated Dilatation (FMD). The meta-analysis revealed that LESWT improved the IIEF-5 score (mean difference: 5.16; 95% CI, 1.39-8.93; p=0.0073) and EHS score (risk difference:0.72; 95% CI, 0.73-0.80; p<0.001). Reporting of FMD was inconsistent and not analyzed. The meta-analysis of studies conducted with electrohydraulic devices showed greater benefits to patients in comparison to the meta-analyses of heterogeneous studies conducted using various devices for generating shock waves. CONCLUSIONS: Evidence exists that LESWT generated with an electrohydraulic unit is effective. Further research is needed in order to evaluate this method in different patient populations and for the long-term.

OBJETIVOS:  Más del 50% de los hombres ancianos y más del 70% de hombres con enfermedades cardiacas sufren de disfunción eréctil (DE). Aunque la farmacoterapia es efectiva y segura, solo conlleva una mejoría temporal y puede causar efectos secundarios. La terapia con ondas de choque de baja energía (OCBE) es una técnica prometedora para el tratamiento de la DE. La evidencia es aún limitada con resultados diferentes obtenidos con aparatos diferentes. El objetivo de este trabajo es evaluar la evidencia de ensayos randomizados en relación a OCBE generado con unidades electrohidráulicas para el tratamiento de la DE.MÉTODOS: Una revisión sistemática de la literatura fue conducida en PubMed el 20 mayo 2018 y suplementada por la búsqueda de Google en literatura gris. También se hicieron búsquedas individuales de artículos. De 34 estudios, 5 estudios en 354 pacientes fueron incluidos para la síntesis cuantitativa. RESULTADOS: Los estudios evaluaron abridged International Index of Erectile Function (IIEF-5), Erectile Hardness Scale (EHS) y Flow-Mediated Dilatation (FMD). El metanálisis reveló que OCBE mejoró el score de IIEF-5 (diferencia media: 5,16; 95% CI, 1,39-8,93;p=0,0073) y EHS score (diferencia de riesgo: 0,72;95% CI, 0,73-0,80; p<0,001). Los reportes de FMD fueron inadecuados y no se analizaron. El metanálisis de estudios conducidos con aparatos electrohidráulicos demostró mayores beneficios a pacientes en comparación con el metanálisis de estudios heterogéneos conducido utilizando varios aparatos generadores de ondas. CONCLUSIONES: La evidencia demuestra que OCBE generado por una unidad electrohidráulica es efectiva. Es necesaria más investigación para poder evaluar este método en diferentes poblaciones de pacientes y para el largo plazo.

Diagnosis of hypogonadism in patients treated with low energy shock wave therapy for erectile dysfunction: a narrative review.

Several methods of treatment of erectile dysfunction (ED) are offered with low energy shock-wave therapy (LESWT) gaining increasing attention. Reports have documented that LESWT stimulates tissue neovascularization, proliferation and differentiation of endothelial cells, and production of nitric oxide - all can improve the condition of erectile tissue. However, the overall and sexual condition of men deteriorates with age which is linked with a constant decrease in testosterone concentration. A higher risk of sexual health disorders and reduced physical fitness correlates with a testosterone concentration of <12 nmol/L. Such patients may require testosterone replacement therapy. We conducted a target literature review to investigate whether testosterone concentration is taken into account in studies on the use of LESWT in the treatment of ED. We found that most studies did not provide any information on testosterone status. Only 8 of 25 studies examined showed values of testosterone concentrations. Only one of these analyses checked the relationship between the efficacy of LESWT and testosterone concentration. As a result, meta-analyses published to date may not show the full value of LESWT in the treatment of ED. We conclude that in the light of the significant role testosterone plays in the process of an erection and the mechanism of LESWT action, it can be recommended to examine testosterone concentration and to diagnose hypogonadism during the qualification of patients to studies on LESWT efficacy. Moreover, the effectiveness of LESWT in relation to the current testosterone concentration should also be further investigated.

A promising therapeutic option for diabetic bladder dysfunction: Adipose tissue-derived stem cells pretreated by defocused low-energy shock wave.

Adipose tissue-derived stem cells (ADSCs) have shown effectiveness in treating diabetic bladder dysfunction (DBD). In the present study, ADSCs pretreated by defocused low-energy shock wave (DLSW) were first used to achieve better therapeutic effect. ADSCs were treated by DLSW prior to each passage. Secretions of vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) were tested. Proliferation ability was examined by staining 5-ethynyl-2-deoxyuridine (EdU) and assessing expressions of proliferating cell nuclear antigen (PCNA) and Ki67. DBD rat model was created and subgrouped via therapeutic options of phosphate-buffered saline, ADSCs, pretreated ADSCs, and ADSCs lysate. Afterward, voiding functions were evaluated, and tissues were examined by histology. Neonatal rats received intraperitoneal injection of EdU. All rats were subgrouped and treated as narrated above. Bladder tissues were stained with EdU, Stro-1, and CD34. Results showed that shocked ADSCs were activated by secreting more VEGF and NGF, by higher EdU-retaining cells ratios, and by higher expressions of PCNA and Ki67 compared with unshocked ADSCs. Shocked ADSCs had the most effective efficacy in treating DBD by secreting the most VEGF and NGF to accelerate regenerations of revascularization and innervation. Migrations of EdU+ Stro-1+ CD34- endogenous stem cells to bladders were enhanced by injecting ADSCs. In conclusion, ADSCs pretreated by DLSW had potent therapeutic effect in treating DBD by secreting VEGF and NGF. Recruitment of endogenous stem cells was considered as an important mechanism in this regenerative process.

The protective effect of low-energy shock wave on testicular ischemia-reperfusion injury is mediated by the PI3K/AKT/NRF2 pathway.

AIMS: Testicular ischemia-reperfusion (IR) injury is the primary pathophysiological consequence of testicular torsion. Low-energy shock wave (LESW) is an effective treatment for certain diseases. The present study investigated whether LESW could improve on testicular IR injury in rats and examined the involved mechanism. MAIN METHODS: Testicular reperfusion was induced in rats after 1-h ischemia. The first LESW treatment was performed 30 min prior to testicular reperfusion, and then every other day for another 3 applications. LY294002 was applied to investigate the involved mechanism. Testicular morphological changes and malonaldehyde (MDA) level were respectively assessed by hematoxylin-eosin staining. Western blot and thiobarbituric acid method. Western blot, real-time quantitative PCR and immunohistochemistry were performed to assess the apoptosis, the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) pathway the nuclear factor erythroid 2-related factor 2 (NRF2) and vascular endothelial growth factor A (VEGF-A) level in the testis of rats. KEY FINDINGS: LESW improved testicular IR injury in rats. Moreover, LESW upregulated the phosphorylation levels of AKT and glycogen synthase kinase 3ß (GSK-3ß). Also, it upregulated the levels of nuclear NRF2, heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO-1) in these rats. Nevertheless, LY294002 blocked these protective effects. LESW also upregulated VEGF-A level in rats with testicular IR injury. SIGNIFICANCE: This study demonstrated that LESW could ameliorate testicular IR injury in rats, which might be attributed to the activation of PI3K/AKT/NRF2 pathway. These findings suggested the potential of LESW in the treatment of testicular torsion.

Endogenous Stem Cells Were Recruited by Defocused Low-Energy Shock Wave in Treating Diabetic Bladder Dysfunction.

Defocused low-energy shock wave (DLSW) has been shown effects on activating mesenchymal stromal cells (MSCs) in vitro. In this study, recruitment of endogenous stem cells was firstly examined as an important pathway during the healing process of diabetic bladder dysfunction (DBD) treated by DLSW in vivo. Neonatal rats received intraperitoneal injection of 5-ethynyl-2-deoxyuridine (EdU) and then DBD rat model was created by injecting streptozotocin. Four weeks later, DLSW treatment was performed. Afterward, their tissues were examined by histology. Meanwhile, adipose tissue-derived stem cells (ADSCs) were treated by DLSW in vitro. Results showed DLSW ameliorated voiding function of diabetic rats by recruiting EdU+Stro-1+CD34- endogenous stem cells to release abundant nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). Some EdU+ cells overlapped with staining of smooth muscle actin. After DLSW treatment, ADSCs showed higher migration ability, higher expression level of stromal cell-derived factor-1 and secreted more NGF and VEGF. In conclusion, DLSW could ameliorate DBD by recruiting endogenous stem cells. Beneficial effects were mediated by secreting NGF and VEGF, resulting into improved innervation and vascularization in bladder.

Combination of low-energy shock-wave therapy and bone marrow mesenchymal stem cell transplantation to improve the erectile function of diabetic rats / 亚洲男科学杂志(英文版)

Stem cell transplantation and low-energy shock-wave therapy (LESWT) have emerged as potential and effective treatment protocols for diabetic erectile dysfunction. During the tracking of transplanted stem cells in diabetic erectile dysfunction models, the number of visible stem cells was rather low and decreased quickly. LESWT could recruit endogenous stem cells to the cavernous body and improve the microenvironment in diabetic cavernous tissue. Thus, we deduced that LESWT might benefit transplanted stem cell survival and improve the effects of stem cell transplantation. In this research, 42 streptozotocin-induced diabetic rats were randomized into four groups: the diabetic group (n = 6), the LESWT group (n = 6), the bone marrow-derived mesenchymal stem cell (BMSC) transplantation group (n = 15), and the combination of LESWT and BMSC transplantation group (n = 15). One and three days after BMSC transplantation, three rats were randomly chosen to observe the survival numbers of BMSCs in the cavernous body. Four weeks after BMSC transplantation, the following parameters were assessed: the surviving number of transplanted BMSCs in the cavernous tissue, erectile function, real-time polymerase chain reaction, and penile immunohistochemical assessment. Our research found that LESWT favored the survival of transplanted BMSCs in the cavernous body, which might be related to increased stromal cell-derived factor-1 expression and the enhancement of angiogenesis in the diabetic cavernous tissue. The combination of LESWT and BMSC transplantation could improve the erectile function of diabetic erectile function rats more effectively than LESWT or BMSC transplantation performed alone.

Efficacy of low energy shock-wave therapy generated using an electrohydraulic device in the treatment of ed: a systematic review and meta-analysis of randomized controlled trials / Eficacia de la terapia de ondas de choque de baja energía generada usando undispositivo electrohidráulico en el tratamiento de la disfunción eréctil: una revisión sistemáticay metanálisis de ensayos controlados aleatorios

Objectives: Over 50% of elderly menand 70% of male cardiac patients suffer from erectiledysfunction (ED). Although pharmacotherapy is effectiveand safe, it only brings a short-term improvement andmay cause side effects. Low energy shock-wave therapy(LESWT) is a promising causative modality for the treatment of ED. The evidence is still limited with differentresults obtained using different devices. The aim of thiswork was to evaluate evidence from randomized controlled trials regarding the efficacy of LESWT generatedby an electrohydraulic unit for the treatment of ED. Methods: A systematic review of the literature wasconducted in PubMed on May 20th, 2018 and supplemented by a Google search of grey literature, aswell as a hand search of the bibliographies of retrievedarticles. Out of 34 studies, 5 studies on 354 patientswere included in the quantitative synthesis.Results: The studies evaluated an abridged International Index of Erectile Function (IIEF-5), the Erectile Hardness Scale (EHS) and Flow-Mediated Dilatation (FMD).The meta-analysis revealed that LESWT improved theIIEF-5 score (mean difference: 5.16; 95% CI, 1.398.93; p=0.0073) and EHS score (risk difference:0.72; 95% CI, 0.73-0.80; p<0.001). Reporting ofFMD was inconsistent and not analyzed. The meta-anal-ysis of studies conducted with electrohydraulic devicesshowed greater benefits to patients in comparison to themeta-analyses of heterogeneous studies conducted usingvarious devices for generating shock waves.Conclusions: Evidence exists that LESWT generated with an electrohydraulic unit is effective. Further research is needed in order to evaluate this method indifferent patient populations and for the long-term

Objetivo: Más del 50% de los hombresancianos y más del 70% de hombres con enfermedades cardiacas sufren de disfunción eréctil (DE). Aunquela farmacoterapia es efectiva y segura, solo conllevauna mejoría temporal y puede causar efectos secundarios. La terapia con ondas de choque de baja energía(OCBE) es una técnica prometedora para el tratamientode la DE. La evidencia es aún limitada con resultadosdiferentes obtenidos con aparatos diferentes. El objetivo de este trabajo es evaluar la evidencia de ensayosrandomizados en relación a OCBE generado con unidades electrohidráulicas para el tratamiento de la DE. Materiales y métodos: Una revisión sistemática de la literatura fueconducida en PubMed el 20 mayo 2018 y suplementada por la búsqueda de Google en literatura gris. También se hicieron búsquedas individuales de artículos.De 34 estudios, 5 estudios en 354 pacientes fueronincluidos para la síntesis cuantitativa. Resultados: Los estudios evaluaron abridged International Index of Erectile Function (IIEF-5), Erectile Hardness Scale (EHS) y Flow-Mediated Dilatation (FMD).El metanálisis reveló que OCBE mejoró el score deIIEF-5 (diferencia media: 5,16; 95% CI, 1,39-8,93;p=0,0073) y EHS score (diferencia de riesgo: 0,72;95% CI, 0,73-0,80; p<0,001). Los reportes de FMDfueron inadecuados y no se analizaron. El metanálisisde estudios conducidos con aparatos electrohidráulicosdemostró mayores beneficios a pacientes en comparación con el metanálisis de estudios heterogéneos conducido utilizando varios aparatos generadores de ondas. Conclusiones: La evidencia demuestra que OCBEgenerado por una unidad electrohidráulica es efectiva.Es necesaria más investigación para poder evaluar estemétodo en diferentes poblaciones de pacientes y parael largo plazo.(AU)