Injection Of Prostaglandin E2 Research Articles

Effects of PGE1 on the ERS pathway in neonatal rats with hyperoxic lung injury.

With the increase in the number of low birth weight infants, oxygen therapy is more widely used. However, chronic high-concentration oxygen environments lead to hyperoxic lung injury in children, which in turn leads to bronchopulmonary dysplasia (BPD). PGE1 is widely used in the clinic for its ability to inhibit inflammation and improve circulation. Therefore, we further investigated whether PGE-1 has a therapeutic effect on hyperoxic lung injury. Hyperoxic lung injury model was adopted for investigating the interventional effects and underlying mechanisms of intraperitoneal injection of prostaglandin E1 (PGE-1) on hyperoxic lung injury in newborn rats via relevant experimental techniques, such as Diff-Quick staining, lung wet dry specific gravity measurements, HE staining, TUNEL staining, ELISA, and the Western blot method. Inflammatory and apoptotic cells in the PGE1-treated group were significantly lower than those in the hyperoxic lung injury group (p < 0.05); and the contents of IL-1β, IL-6 and TNF-α in the treated group were significantly lower than those in the model group (p < 0.05). Caspase-3, CHOP, GRP78 and Bcl-2/Bax protein expression in the treatment group was significantly lower than that in the model group (p < 0.05). PGE-1 has a therapeutic effect on hyperoxic lung injury in neonatal rats. PGE1 treatment reduces levels of inflammatory cells and pro-inflammatory cytokines and decreases apoptosis. PGE1 has a therapeutic effect on BPD through the endoplasmic reticulum stress pathway. This study offers the possibility of PGE1 for the treatment of BPD.

Evaluation of platelet-rich fibrin matrix combined with PGE-1 injection on erectile function in patients with refractory response to PDE5-I: a randomized placebo-controlled study.

We studied the effect of a platelet-rich fibrin matrix (PRFM) combined with prostaglandin E-1 (PGE-1) injection on erectile function in patients refractory to response for phosphodiesterase type 5 inhibitors (PDE5-Is). This randomized, double-blind, placebo-controlled study included 80 patients. The patients were randomly assigned to four groups and blinded together with the administrating physicians to the nature of the intracorporeal injection (ICI) therapies. Group (1) received saline, group (2) received platelet-rich fibrin matrix (PRFM), group (3) received prostaglandin E-1 (PGE-1), and group (4) received a combination of PRFM + PGE-1. The patients received ICI therapy weekly for 8 consecutive weeks. Clinical information and follow-up data were obtained at 1, 2, 3, and 6months. A significant increase occurred in the validated Arabic version of the International Index of Erectile Function (ArIIEF-5) score in group (4) compared to the other three groups (p value = 0.037). There was a significant difference in erection hardness scale (EHS) scores among all groups after receiving the different treatments (p = 0.004). A significant increase was seen in the ArIIEF-5 score in groups 4 and 3 compared to that in groups 1 and 2 (p < 0.001). There was also a significant increase in the arterial dilatation % in groups 4 and 3 compared to that in groups 1 and 2 (p = 0.019). The combination of PRFM plus PGE-1 had shown significant improvement in the ArIIEF-5 score, yet the patients still had mild to moderate ED.

Does MRI Have a Role in the Preoperative Staging of Penile Cancer?

Background Penile cancer is a rare malignancy usually requiring surgery to achieve oncological control of the primary tumour but often at the expense of functional length. The presenting stage of the primary is a crucial factor in determining the most appropriate surgical procedure. Accurate preoperative staging is essential, and current modalities include clinical and radiological assessment. Clinical staging can, however, be hampered by patient body habitus and unreliable for more advanced T4 tumours, whereas radiological staging allows for more detailed identification of tissue planes and tumour involvement. There is no clear consensus on the preferred imaging technique, although, in the current European Association of Urology penile cancer guidelines, MRI is recommended with the use of ultrasound when MRI is not available. It was recommended that having the penis in an erect state by the administration of intra-cavernosal prostaglandin gave a more detailed picture enabling a greater predictor of corporal involvement. Recent studies have, however, suggested that there may be no such advantage. Methodology A retrospective review was conducted of all patients who underwent surgery for penile cancer comparing the preoperative MRI stage with the final pathological stage between July 2009 and June 2023.In addition to the MRI, patients were given an intra-cavernosal injection of prostaglandin E1 to induce tumescence unless otherwise indicated. All imaging was reported by a single consultant uro-radiologist with surgery undertaken by a single surgeon and pathology reviewed through the supra-regional penile multidisciplinary team. Results A total of 136 penile cancer patients were included in the review. Within this cohort, 98 patients had an MRI without intra-cavernosal prostaglandin and the number who had Ta, T1, T2, T3 and T4 histopathological stages was 3, 31, 45, 18, and 1, respectively. The preoperative MRI stage had a low agreement with the final histological stage for early tumours, with sensitivities and specificity of 35% and 97% for T1 and 56% and 80% for T2, respectively. Sensitivity and specificity increased for cavernosal involvement at 83% and 95%, respectively. In addition, a further 38 patients had an MRI in conjunction with an injection of prostaglandin E1 which failed to show any diagnostic improvement in sensitivity or specificity in the preoperative MRI stage. Conclusions The use of MRI as a preoperative modality for staging penile cancer performs best for identifying tumour involvement of the cavernosal bodies. Performing the MRI with the penis erect with the use of an intra-cavernosal injection did not offer any additional benefit in accurately staging penile cancer.

(100) Cavernovenous Leakage: A New Surgical Treatment in 171 Consecutive Patients with Severe, Drug-Resistant Erectile Dysfunction

Abstract Introduction Cavernovenous leakage (CVL) is a frequent cause of erectile dysfunction (ED) in which blood entering corpora cavernosa escapes too early due to abnormal venous network, for erections to develop or maintain. When PDE5Is are ineffective to compensate for leakage, CVL is a devastating condition, affecting millions worldwide for whom no specific treatment is currently proposed. Objective Evaluate results of a new method of treatment combining open surgery and embolization simultaneously during the same procedure, in patients with CVL resistant to PDE5Is. Methods 171 consecutive patients with severe ED for more than six months, with CVL diagnosed by pharmacologically-challenge penile duplex sonography (PC-PDS) using intracavernous injection of Prostaglandin E1 and Papaverine, were operated-on. Leaks were imaged by caverno-computed tomography. Patient with other cause of ED were excluded, all had refused a penile implant, signed an informed consent, had a control PC-PDS three months after surgery, and were clinically evaluated during follow-up. A retrospective analysis was performed on prospectively collected data. Comparisons of variables before and after surgery used a paired t-test. Results Mean age was 43.8±13.6 years, range 18–76. ED had started at the beginning of sexual life (30) in 47.4%. Mean ED duration before surgery was 11.1±9.1 years (range 0.5–30). All patients had two clinical signs of organic ED: 1. no phase of erection improvement in the past six months, 2. erection alterations during masturbation (Erection Hardness Score (EHS)&amp;lt;3 and/or erection instability). Signs suggesting CVL were 1. variation of erection hardness according to position during masturbations or intercourses in 59.1%, 2. erections instability during masturbation or intercourse in all patients. At three-month evaluation, mean pharmacologic EHS had increased from 2.56±.66 before surgery, to 3.40±.56 (p&amp;lt;.0001). All CVL hemodynamic parameters at PC-PDS had decreased compared to pre-surgery: mean End Diastolic Velocity (from 16.6±9.5 to 9.3±7.7 cm/s, p&amp;lt;.0001), mean leakage speed on Deep Dorsal Vein (from 12.8±13.4 to .8±3.2 cm/s, p&amp;lt;.0001), mean speed on any superficial vein (from 11.2±10.1 to 3.9±6.3 cm/s, p&amp;lt;.0001). Patients unable to perform penetrations despite ICC injection of Prostaglandin E1 20 micg plus Papaverine 40 mg (EHS&amp;lt;3) decreased from 66.9 to 11.6% (p&amp;lt;.001). At the end of the 29.8±20.4-month follow-up, IIEF-5 score had increased from 9.7±5.1 to 15.5±6.0 (p&amp;lt;.0001), clinical EHS during sexual intercourse from 2.0±.7 to 3.3±.7 (p&amp;lt;.0001), penetration success rate from 22.3±31,7 to 70.1±37.2% (p&amp;lt;.0001), mean EHS during masturbation from 2.11±.67 to 3.04±.75 (p&amp;lt;.0001), EHS at morning erection from .95±1.24 to 2.1±1.37 (p&amp;lt;.0001), before and after surgery, respectively. 30.4% did not take any medication for erection. Success rate defined by post-operative EHS&amp;gt;3 and/or EHS increase &amp;gt;0.5 and erection stability was 80.7%. 78.9% recognized sexual support by a sexual medicine specialist is necessary for sexual recovery after surgery. Conclusions Simultaneous open surgery and embolization is a new procedure that offers unprecedented documented results in CVL resistant to PDE5Is. Clinical screening of CVL in ED patients is simple and should be evaluated in sexual medicine practice. Disclosure No.

(036) The Comparison of an Efficacy and Safety of Geometrical Principles Based Corporoplasty Combined with Intraoperative Intracavernosal Prostaglandin E1 Injections and the Non-Geometrical Surgical Techniques for Peyronie's Curvature Correction

Abstract Introduction There is a lack of research evidence and properly conducted comparative long-term studies in regards to whether the intra and post-operative safety and efficacy of geometrical principle of plaque incision and grafting technique, especially if combined with an intraoperative intracavernosal prostaglandin E1 (PGE1) injection instead of saline, is better than the non-geometrical techniques. Objective The aim of this retrospective study was to present our 8-year single-center experience of surgical management of Peyronie's disease in the means of efficacy and safety by comparing geometrical principle of plaque incision and grafting technique combined with the intraoperative intracavernosal PGE1 injection with the other non-geometrical surgical techniques used at our centre for the treatment of penile curvature. Methods Our andrology centre approved this retrospective study and commenced an audit in order to obtain anonymised data. In total 70 patients underwent non-geometrical surgical techniques based penile curvature correction between 2014 and 2017. All the surgeries were carried out performing the intraoperative intracavernosal PGE1 injection instead of obtaining saline-induced erection. The demographic data was retrieved and a comparative analysis was performed. Results In total 216 (N=216) patients, aged 42–73 years old (average age 59 years) suffering from Peyronie's disease had surgical treatment of the curvature at our centre from 2014 to 2023. Group 1 (G1) patients accounted for 32.41% (N=70) of total patients - they were 46–78 years old (average age 64 years) and underwent non-geometrical principals based surgery for Peyronie's disease in between 2014 and 2017. Group 2 (G2) patients accounted for 68.52% (N=148) of total patients - they underwent the surgery using plaque's incision and grafting technique based on geometrical principles in between 2018 and 2023. 31 patients (44.3%) out of G1 required additional curvature corrections after an initial surgery, but only 3 patients (2.0%) out of G2 required that. Preoperative dorsal penile curvature degree among G1 was 50° - 100° (the mean degree 70°) and 60° - 110° (the mean degree 78°) among G2. 11 patients (15.7%) out of G1 and 15 patients (10.1%) out of G2 had the combined dorsolateral curvature. 3 patients (4.3%) out of G1 and 6 patients (4.1%) out of G2 had ventral curvature. 9 patients (12.9%) out G1 and 2 patients (1.4%) out of G2 have reported a subjective statement of their penile shaft appearing shorter after the curvature correcting surgery. 2 patients (2.9%) out G1 and 1 patient (0.7%) out of G2 have reported a subjective statement of erectile dysfunction post the surgery. There were no intraoperative or postoperative complications associated with the intracavernosal PGE1 injection. Conclusions In summary, we found that plaque's incision and grafting technique based on geometrical principles was advantageous against the other non-geometrical penile curvature surgical techniques due to better efficiency achieved by the higher initial success rates that require an additional correction almost twice less often. We also revealed that the intracavernosal PGE1 injection was a safe and sufficient method for inducing erection intraoperatively, that had not been associated with any complications and maintained the good outcomes of the surgical Peyornie's disease treatment. Disclosure No.

(235) False Negative Penile Duplex Sonography: Results of Cavernovenous Leakage Surgery in 41 Patients with Normal End-Diastolic Velocity. The Need for Venous Leak Hemodynamic Criteria Re-Evaluation?

Abstract Introduction In cavernovenous leakage (CVL), blood entering corpora cavernosa escapes too early due to abnormal venous network, for erections to develop or maintain. CVL diagnosis relies on persisting blood flow velocity in cavernosal arteries at the end of diastole (EDV), with a consensus 5 cm/s cut-off value at pharmacologically-challenged penile duplex sonography (PC-PDS). Objective We present clinical, hemodynamic characteristics, and response to surgery of 41 patients with severe ED resistant to PDE5Is, with EDV5 cm/s at PC-PDS, considered non pathologic, but with CVLs identified by gold standard pharmacologically-challenged penile CT-cavernography. Methods Prospectively collected data from 41 consecutive patients with ED resistant to PDE5Is, with cavernosal artery EDV5 cm/s (Group A), were compared to data from 130 patients with EDV&amp;gt;5 cm/s (Group B). CVLs in Group A were detected by PC-PDS on deep dorsal vein or penile superficial veins after intracavenosal injection of Prostaglandin E1 plus Papaverine. All patients had refused a penile implant and underwent CVL intervention consisting in open surgery and embolization during the same procedure. Inter-group comparison used a T-test of means, pre- and post-operative data comparison a paired t-test. Results Patients in Group A were younger than in Group B (mean age 38.2±14.0 and 45.9±11.6 years, respectively, p&amp;lt;.0022). Pharmacologic Erection Hardness Score (EHS) was higher (2.9±.7 vs. 2.4±.6, p&amp;lt;.0001), EDV velocity was less (1.6±2.2 vs. 15.1±2.2 cm/s, p&amp;lt;.0001) in Group A than B, respectively. Pre-operative IIEF5 score was higher in Group A than in B (13.3±5.3 and 9.4±4.8, respectively, p&amp;lt;.0181). Other pre-operative erection parameters were otherwise similar in the two groups (morning erection EHS and frequency, masturbation and sexual intercourse EHS, percentage of successful penetration (p&amp;lt;.498, .543, .682, .510, .289, respectively). Patients in Group A and B responded similarly to surgery, with a similar pharmacologic EHS increase at systematic three-month post-operative PC-PDS (0.77±.94 vs. .81±.67, p&amp;lt;.80). Mixing Group A and B 171 patients, at the end of the 29.8±20.4-month follow-up, a significant improvement on all clinical parameters was observed: IIEF-5 score had increased from 9.7±5.1 to 15.5±6.0 (p&amp;lt;.0001), clinical EHS during sexual intercourse from 2.0±.7 to 3.3±.7 (p&amp;lt;.0001), penetration success rate from 22.3±31.7 to 70.1±37.2% (p&amp;lt;.0001), mean EHS during masturbation from 2.11±.67 to 3.04±.75 (p&amp;lt;.0001), morning erection EHS from .95±1.24 to 2.12±1.37 (p&amp;lt;.0001), before and after surgery, respectively. There was no statistically significant difference between Group A and B regarding all these parameters, demonstrating similar clinical responses to surgery. Conclusions Patients with EDV5 cm/s may have CVL evidenced by PC-PDS flow analysis directly on veins, and gold standard PC-PCTC. Their erection disability is severe. They respond well to combined open and embolization surgery, a confirmation that they suffer CVL. EDV criterium misses CVL in as much as one patient out of four with actual CVL in our series. Since false negative diagnosis has severe, life-long, patient and partner implications, hemodynamic criteria for CVL diagnosis should be debated in the field of sexual medicine. Disclosure No.

(157) Primary Erectile Dysfunction Caused by Cavernovenous Leakage: Clinical Presentation and New Surgical Treatment in 81 Consecutive Patients with Severe Erectile Dysfunction

Abstract Introduction Introduction. Primary erectile dysfunction (PED) due to cavernovenous leakage (CVL), a disease in which blood entering corpora cavernosa escapes too early because of abnormal venous network, may affect as many as 1 to 2% of men under 30 with failure of erections to develop or maintain. When resistant to PDE5Is, it is a devastating condition leaving men with no possibility of sexual intercourse with penetration, and usually absence of diagnosis and specific treatment. Objective Evaluate symptoms and results of a new method of treatment combining open surgery and embolization simultaneously during the same procedure, in patients with PED and CVL resistant to PDE5Is. Methods 81 consecutive patients with severe PED with CVL diagnosed by pharmacologically-challenge penile duplex sonography (PC-PDS) were operated-on. Leaks were imaged by caverno-computed tomography. Patients with other cause of ED were excluded, all had refused a penile implant, signed an informed consent, had a control PC-PDS three months after surgery, and were clinically evaluated during follow-up. A retrospective analysis was performed on prospectively collected data. Comparisons of variables before and after surgery used a paired t-test. Results Mean age at PED onset reported by patients was 19.0±4.6 years, range 13–30. Mean age at surgery was 34.5±9.2 years, range 18–70. Mean ED duration before surgery was 15.4±10.1 years (range 1–40). All patients had clinical signs of organic ED (no phase of erection improvement in the past six months, erectile dysfunction during masturbation (Erection Hardness Score (EHS)&amp;lt;3 and/or erection instability). CVL could be suspected in all patients based on reported erection instability during masturbation, and in 86.4%, based on variation of EHS according to body position during masturbations. At three-month evaluation, mean pharmacologic EHS had increased from 2.59±.77 before surgery, to 3.45±.63 (p&amp;lt;.0001). The mean pharmacologic EHS increase was 0.83±.92. All CVL hemodynamic parameters at PC-PDS had decreased compared to pre-surgery: mean End Diastolic Velocity (from 9.9±9.22 to 6.77±7.34 cm/s, p&amp;lt;.023), mean leakage speed on Deep Dorsal Vein (from 10.87±12.48 to .69±2.77 cm/s, p&amp;lt;.0001), mean speed on any superficial vein (from 10.96±10.08 to 4.77±6.90 cm/s, p&amp;lt;.0001). Patients unable to perform penetrations despite intracavernous injection of Prostaglandin E1 20 micg plus Papaverine 40 mg (pharmacological EHS&amp;lt;3) decreased from 64.2 to 13.5% (Chi-square test: p&amp;lt;.001). At the end of the 26.0±21.9-month follow-up, IIEF-5 score had increased from 8.9±5.3 to 16.1±5.8 (p&amp;lt;.013), clinical EHS during sexual intercourse from 1.97±.67 to 3.31±.71 (p&amp;lt;.0001), penetration success rate from 18.3±28.2 to 64.2±40.1%, morning EHSfrom 1.11±1.40 to 2.12±1.49 (p&amp;lt;.0002), masturbation EHS from 2.14±.84 to 3.07±.77 (p&amp;lt;.002) before and after surgery, respectively. 38.3% did not take any medication for erection. Conclusions Simultaneous open surgery and embolization is a conservative treatment that should be discussed for patients with PED and CVL. PED can be suspected during consultation. Detection of CVL in all patients under 30 with ED should be evaluated in sexual medicine practice. Disclosure No.

The usefulness of shear wave elastography in evaluating erectile dysfunction severity before and after prostaglandin E1 test.

Prostaglandin E1 intracavernous injection test is an established method for diagnosing erectile dysfunction. However, the evaluation is non-objective and often influenced by the evaluator's subjectivity. Herein, we measured and objectively evaluated shear wave elastography results of the corpus cavernosum before and after injection in 16 patients who underwent prostaglandin E1 testing. The response score of prostaglandin E1 tests were "1" in 2 cases, "2" in 2 cases, and "3" in 12 cases. The average transmission velocity before the injection and at the time of maximum erection after the injection were 2.21 m/s and 1.57 m/s, respectively. Transmission velocity decreased during erection in 14 of 16 cases (87.5%). The overall rate of change in transmission velocity due to injection was -26.7% and was significantly different between the poor (responses 1 and 2: -16.1%) and good erection (response 3: -30.2%) groups. To the best of our knowledge, this is the first attempt to evaluate erectile phenomenon using percutaneous ultrasonic elastography in Japan. Rate of change in shear wave transmission velocity due to prostaglandin E1 injection in the corpus cavernosum penis was associated with the degree of erection. Therefore, the rate of change in shear wave transmission velocity in the corpus cavernosum penis could be used as an objective index of erectile phenomenon. Percutaneous ultrasonic elastography is a non-invasive and useful test method for diagnosing erectile dysfunction, determining the therapeutic effect, and predicting prognosis.

ERECTILE DYSFUNCTION TREATMENT USING SUBCUTANEOUS IMPLANTS WITH A LONG-TERM EFFECT

Introduction. The article describes a new method of improving erectile function by incerting long-acting subcutaneous implants with the phosphodiesterase 5 (PDE 5) inhibitor.&#x0D; The aim of the study: To evaluate the effectiveness of tadalafil in the treatment of erectile dysfunction using bioidentical pellets.&#x0D; Materials and methods: The study included 10 men under 65 years of age who had suffered from erectile dysfunction for more than 1 year.&#x0D; For the examination before and 4 months after the intervention, the following were performed: filling out the MIEF-5 questionnaire, phical examination, Doppler of penile vessels, «Erection Hardness Scale», laboratory examination (general and biochemical blood tests, general urine analysis and hormonal testing, including determination of the levels of total testosterone, free testosterone, prolactin, estradiol and dehydroepiandrosterone sulfate.&#x0D; All patients received implants with bioidentical tadalafil 75 mg. The pellet was inserted in a sterile operating room through a 3 mm skin incision in the outer quadrant of the gluteal region and inserting the substance into the subcutaneous fat.&#x0D; Results: All patients showed an improvement in MIEF-5 from 14.7 ± 2.75 to 20.7 ± 1.49, an increase in systolic blood flow velocity and penile rigidity at the tenth minute after prostaglandin E1 injection on Doppler vascular examination.&#x0D; Conclusion: This study demonstrated the efficacy of tadalafil by pellet administration in the treatment of erectile dysfunction in men younger than 65 years.

Electroacupuncture prevents the development or establishment of chronic pain via IL-33/ST2 signaling in hyperalgesic priming model rats

BackgroundChronic pain is acomplexhealth issue. Compared to acute pain, which has a protective value, chronic pain is defined as persistent pain after tissue injury. Few clinical advances have been made to prevent the transition from acute to chronic pain. Electroacupuncture (EA), the most common form of acupuncture, is widely used in clinical practice to relieve pain. MethodsThe hyperalgesic priming model, established via a carrageenan injection followed by a prostaglandin E2 injection, was used to investigate the development or establishment of chronic pain. We observed the hyperalgesic effect of EA on rats and investigated the expression p38 mitogen-activated protein kinase, interleukin-33 (IL-33), and its receptor ST2 in astrocytes in the L4–L6 spinal cord dorsal horns (SDHs) after EA. The IL-33/ST2 signaling pathway in SDH is associated with the development of chronic pain. ResultsEA can reverse the pain threshold in hyperalgesic priming model rats and regulates the expression of phosphorylated p38, IL-33, and ST2 in astrocytes in the L4–L6 SDHs. We discovered that EA raises the pain threshold. This suggests that EA can prevent the development or establishment of chronic pain by inhibiting IL-33/ST2 signaling in the lower central nervous system. ConclusionsEA can alleviate the development or establishment of chronic pain by modulating IL-33/ST2 signaling in SDHs. Our findings will help clinicians understand the mechanisms of EA analgesia.

Arterial stiffness, blood pressure progression and penile vascular disease in males with erectile dysfunction: a closer look at microcirculatory damage

Abstract Background Elevated aortic stiffness may be associated with microvascular remodelling and damage, which may be an important causal contributor to incident cardiovascular disease. Recent evidence supports the independent of age and blood pressure (BP) level predictive value of severe penile arterial insufficiency for adverse cardiovascular events. Purpose Aim of the study is to examine in men with erectile dysfunction the association of increased aortic stiffness with penile vascular damage by taking into account BP level. Methods We measured carotid-femoral pulse wave velocity (PWV) and assessed microvascular (penile vascular damage) changes in four age-matched groups without a history of diabetes and cardiovascular disease; Normal BP (n=137), high-normal BP (n=94), stage I hypertension (n=82) and stage II and III hypertension (n=76). Microvascular damage was examined by measuring penile peak systolic velocity (PSV) with a dynamic penile color Doppler ultrasonography after intracavernous injection of prostaglandin E1. Lower PSV values indicate severe penile vascular disease. Results Carotid-femoral PWV increased and PSV decreased across BP groups (all P&amp;lt;0.001). In regression analysis increased systolic BP (b= -0.185, P&amp;lt;0.01) and PWV (b= -0.170, P&amp;lt;0.05) are significant determinants of low penile PSV after controlling for age, body mass index, cholesterol and smoking. We dichotomized carotid-femoral PWV taking into account the mean value in the whole study population. Figure shows the differences in PSV across the BP groups considering the cut-off PWV value of 8.5m/s (high vs low PWV). Individuals with higher PWV had lower penile PSV in normal BP (P&amp;lt;0.01) and in high normal BP group (P=0.02) after adjusting for age and systolic BP. On the contrary, hypertensive patients already have significant structural damage in the penile arteries and high PWV does not further reduce penile blood flow. Interestingly, figure shows the comparable PSV measurements between individuals with high-normal BP level who had high PWV and patients in stage 1 hypertension group denoting significantly impaired microvascular damage in males with high-normal BP and increased aortic stiffness. The high normal BP group has significantly lower PSV compared to normal BP group independently of PWV value. Conclusion Increased aortic stiffness may promote penile microvascular remodelling and damage in men without increased BP level. Additionally, in men with high-normal BP higher arterial stiffness is associated with comparable penile microvascular damage of men with arterial hypertension. Because aortic stiffening may be preventable, further clinical research on earlier preventive measures that focus on aortic stiffness and microvascular remodelling within individuals with erectile dysfunction who have normal BP is warranted.Aortic stiffness, BP level and PSV

Acute changes of superior mesenteric artery pressure after intraarterial bolus injection of prostaglandin-E1.

Background: A bolus injection of prostaglandin-E1 (PGE1) into the superior mesenteric artery (SMA) immediately before SMA-portography can effectively visualize the portal vein. Objective: The purpose of this study was to obtain basic pharmacoangiographical data and evaluate the hemodynamic changes following intra-arterial bolus injection of PGE1. Materials and Methods: Forty-four consecutive patients undergoing transcatheter arterial chemoembolization (TACE) for liver cancer were retrospectively evaluated. SMA-portography was performed prior to TACE. An intra-arterial bolus injection of PGE1 was performed immediately before SMA-portography. Both SMA pressure and left brachial artery pressure were measured before, 1, 2, 3, 4, and 5 minutes after SMA-portography. Results: Systolic pressure in the SMA decreased significantly 3 minutes after SMA-portography and remained low for 5 minutes. The maximum reduction rates in systolic and diastolic blood pressure in the SMA were 4.8% (4 minutes after SMA-portography) and 6.8% (5 minutes after SMA-portography), respectively. The left brachial artery pressure decreased similarly to the SMA. There were no significant changes in pulse pressure before or after PGE1 injection in either the SMA or brachial arteries. Conclusion: A bolus injection of PGE1 into the SMA was shown to decrease blood pressure in the SMA and brachial arteries, but the pulse pressure remained constant.

Efficacy of prostaglandin E2 versus prostaglandin F2 alpha assisted with narrowband-UVB in stable vitiligo

In the recent decades, prostaglandins were recommended as a new therapeutic modality of stable vitiligo with promising efficacy. Therefore, we designed the current work to compare the significance of two different subtypes of prostaglandins [prostaglandin E2 (PGE2) versus prostaglandin F2 alpha (PGF2α)], assisted with NB-UVB phototherapy, in treatment of stable vitiligo. This study was conducted on 30 patients with stable non-segmental vitiligo. Three approximately similar vitiliginous areas were chosen in each patient and assigned into 3 groups. Each group treated with intradermal injection of either PGE2 (group I), PGF2α (group II), or saline as placebo (group III) at frequency once/week for 12 weeks. Concomitantly, all groups received NB-UVB phototherapy twice weekly for 3 months. The outcomes of this study discovered that the therapeutic efficacy of intradermal injection of either PGE2 or PGF2α assisted with NB-UVB phototherapy was comparable with non-significant difference between them in spite of being significantly higher than NB-UVB alone. However, there were a significantly earlier onset of repigmentation and higher degree of satisfaction regarding areas treated with PGE2 than those treated with PGF2α. In conclusion, both PGF2α and PGE2 intradermal injection could be considered as quite simple and affordable techniques in the treatment of stable vitiligo with no reported side effects and good patient satisfaction.

(161) Xiaflex Nonresponders Show Alteration in Penile Measurements: Post-Market Analysis of Predictors for Treatment Success

Abstract Introduction The IMPRESS trial revealed that intralesional collagenase clostridium histolyticum, Xiaflex, is safe and efficacious for treating the physical and subjective effects of Peyronie’s Disease (PD). However, little is known about the other manifestations of PD, namely penile shortening and efficacy for patients of diverse racial backgrounds or with severe penile curvatures. Objective To evaluate predictors associated with response to treatment and alterations in penile morphological measurements. Methods Consecutive patients treated with Xiaflex for dorsal, lateral, and ventral penile curvatures ≥ 25°, in the absence of hourglass deformity, were included in this study. Before treatment and eight weeks after the last injection cycle, during penile duplex Doppler ultrasound evaluation, penile curvature was measured with a goniometer after induced artificial erection via injection of prostaglandin E1 (PGE1). IIEF score, PGE1 dose, circumference, and erectile as well as stretched penile length were also assessed at these times. Based on the results of the IMPRESS trial, patients were considered Xiaflex responders if the decrease in their penile curvature were ≥ 15° (n =134) and Xiaflex nonresponders if the decrease in their penile curvature were &amp;lt; 15° (n =89). Initial measurements were in increments of 5°. Intention to treat analysis was performed. Results Two hundred and twenty-three patients with penile curvature ≥ 25° who received XIAFLEX were included in this study. One hundred and thirty-four patients (60.1%) responded to Xiaflex, while 89 (39.9%) patients did not respond. African American men were 3 times more likely to respond to treatment than their non-African American counterparts (Odds Ratio (OR) =3.35 (95% CI, 1.15-10.70), p =0.031). On the other hand, men with an initial penile curvature of greater than 60° were less likely to respond to Xiaflex (OR = 0.34; 95% CI, 0.16-0.69; p=0.003). However, patients with lateral and ventral curvatures responded at comparable rates to those with dorsal curvatures. Subsequently, changes in penile morphologic measurements post Xiaflex were analyzed. Average stretched penile length, erectile length, and erectile circumference prior to treatment for responders were 13.93 cm, 13.39 cm, and 11.81 cm, respectively; for nonresponders, it was 14.27 cm, 13.72 cm, 11.64 cm, respectively. Nonresponders were shown to experience a significant decrease in penile erect length (-0.55 cm) and circumference (-0.58 cm) (p=0.002 and p=0.002, respectively), whereas responders showed no significant alterations in penile morphologic measurements. Conclusions Our analysis revealed that men with penile curvatures ≥ 60° are less likely to respond to Xiaflex injections and thus may be considered for surgical intervention upon initial presentation. Furthermore, men who do not respond may even be at a higher risk for shortening of penile erect length and circumference. The actual clinical significance of a decrease in average erect length of 0.55 cm and circumference of 0.58 cm is difficult to determine and should be considered per patient preferences. Further investigations into predictors for response to Xiaflex and the pathophysiology behind penile shortening in Xiaflex nonresponders are warranted. Disclosure No

Hydroethanolic Leaf Extract of Cordia vignei Hutch and Dalziel Inhibits Carrageenan-Induced Foot Oedema in Chicks, Prostaglandin E2-Induced Paw Oedema in Mice, and Bradykinin-Induced Paw Oedema in Mice.

Cordia vignei Hutch and Dalziel (Fam. Boraginaceae) is a woody plant found in west tropical Africa. The aim of this research is to find out if the leaf extract of this plant prevents oedema in animal models. (a) Inflammation was induced in the animals by injecting 100 µl of 2% lambda carrageenan into the subplantar tissue of the right footpads of 7-day-old chicks 1 h before or after oral administration of 30-300 mgkg-1 CVE. Oedema was measured for 5 h using the water displacement method. (b) Oedema was induced in ICR mice by subplantar injection of prostaglandin E2 (PGE2) (50 µl of 1 nM) 30 minutes before or after CVE administration. Oedema was measured for 3 h. (c) Oedema was induced in ICR mice by subplantar injection of bradykinin (BK) (10 nmol/paw) 30 min before or after administration of extract. We found that CVE significantly (P < 0.05) prevented inflammation that was induced by injecting carrageenan into the footpads of the chicks. Also, we observed that CVE prevented inflammation produced by injecting PGE2 into the subplantar tissue of mice. Finally, we also report that CVE prevented inflammation produced by injecting BK into the subplantar tissues of mice. All these effects were observed in both preventive and curative protocols. We conclude that Cordia vignei leaf extract has potential anti-inflammatory activity.

Prostaglandin E2 prevents radiotherapy-induced alopecia by attenuating transit amplifying cell apoptosis through promoting G1 arrest

BackgroundGrowing hair follicles (HFs) harbor actively dividing transit amplifying cells (TACs), rendering them highly sensitive to radiotherapy (RT). Clinically, there is still a lack of treatment options for radiotherapy-induced alopecia (RIA). ObjectiveOur present study aimed to investigated the effect and mechanism of local prostaglandin E2 (PGE2) treatment in RIA prevention. MethodsWe compared the response of growing HFs to radiation with and without local PGE2 pretreatment in a mouse model in vivo. The effect of PGE2 on the cell cycle was determined in cultured HF cells from fluorescent ubiquitination-based cell cycle indicator mice. We also compared the protective effects of PGE2 and a cyclin-dependent kinases 4/6 (CDK4/6) inhibitor against RIA. ResultsThe local cutaneous PGE2 injection reduced RIA by enhancing HF self-repair. Mechanistically, PGE2 did not activate HF stem cells, but it preserved more TACs for regenerative attempts. Pretreatment of PGE2 lessened radiosensitivity of TACs by transiently arresting them in the G1 phase, thereby reducing TAC apoptosis and mitigating HF dystrophy. The preservation of more TACs accelerated HF self-repair and bypassed RT-induced premature termination of anagen. Promoting G1 arrest by systemic administration of palbociclib isethionate (PD0332991), a CDK4/6 inhibitor, offered a similar protective effect against RT. ConclusionsLocally administered PGE2 protects HF TACs from RT by transiently inducing G1 arrest, and the regeneration of HF structures lost from RT is accelerated to resume anagen growth, thus bypassing the long downtime of hair loss. PGE2 has the potential to be repurposed as a local preventive treatment for RIA.

Integrating Spatial Transcriptomics and Single-nucleus RNA Sequencing Reveals the Potential Therapeutic Strategies for Uterine Leiomyoma.

Uterine leiomyoma is the most common gynecological tumor in reproductive women. Tumor-host interface is a complex ecosystem with intimate cell-cell communications and a critical scenario for tumor pathogenesis and progression. The pseudocapsule is the main tumor-host interface of uterine leiomyoma, but its cellular spatial disposition and gene expression are poorly explored. This study mapped the cellular architecture and corresponding gene profiles of the leiomyoma and its surrounding pseudocapsule by integrating spatial transcriptomics and single-nucleus RNA-sequencing at the first time. Here, we reported that estrogen receptor alpha and progesterone receptor mediated the occurrence and development of uterine leiomyoma and that estrogen receptor beta involved in the angiogenesis, which explained the effectiveness of hormonotherapy. Therapeutic targets including ERK1/ERK2 pathway and IGF1-IGF1R were found and might be applied for non-hormonal therapy of uterine leiomyoma. Furthermore, the injection of prostaglandin E2 was initially presented for bleeding control during myomectomy, injection site should be located at the junction between pseudocapsule and leiomyoma, and surrounding pseudocapsule should not be eliminated. Collectively, a single-cell and spatially resolved atlas of human uterine leiomyoma and its surrounding pseudocapsule was established. The results revealed potentially feasible strategies for hormonotherapy, non-hormonal targeted therapy and bleeding control during myomectomy.

Prostaglandin E2 involvement in the reproduction of small abalone, Haliotis diversicolor

Prostaglandin E2 (PGE2) has been reported to be involved in reproduction as one of the most abundant and widely distributed prostaglandins in invertebrates. Regulating gonad development and gamete production in mollusks can greatly assist artificial breeding, which is believed to promote the commercial benefits of various mollusk species. In the present study, the contents of PGE2 in the gonads of abalone at different developmental stages (maturing stage, ripe stage, and spawning stage) and reproduction states (before and after spawning) were measured. A higher PGE2 level was found in the gonads of abalones at the ripe stage than other stages, and the highest PGE2 level was detected in the ovaries of female H. diversicolor in the UV-stimulated group. Then the effects of PGE2 injection on the spawning efficiency were explored, and the gamete emission rates of female and male abalone were significantly increased after PGE2 injection. Through qRT-PCR and in situ hybridization assay, higher expression levels and wide distribution of phospholipase A2 (PLA2), cyclooxygenase 2 (COX2), prostaglandin E synthases (PGES2), and prostaglandin E2 receptor 4 (EP4) in the gonads of H. diversicolor were observed after spawning. It is speculated that PGE2 may promote the reproductive cycle in both male and female H. diversicolor, although the regulation mechanism of PGE2 in female and male abalone might be different. The results will be useful for the application of PGE2 in the abalone aquaculture practices to increase the reproduction efficiency in future.

Intervention mechanism of electroacupuncture on the EP1-TRPV1 pathway in the dorsal root ganglion of rats in the transition from acute to chronic pain

Intervention mechanism of electroacupuncture on the EP1-TRPV1 pathway in the dorsal root ganglion of rats in the transition from acute to chronic pain

Hyaluronic acid injection for the management of peyronie's disease

To report our findings in terms of safety and efficacy of intralesional injections of hyaluronic acid (IIHA) in the treatment of Peyronie's disease (PD). Data were extrapolated from a single centre prospectively maintained database. 18 patients with PD received IIHA using the same procedure as for collagenase clostridium histolyticum. Penile curvature assessed through Intracavernosal injection of prostaglandin E1, Peyronie's Disease Questionnaire (PDQ) and the International Index of Erectile Function (IIEF) were carried out at baseline and at week 7. The Global Assessment of Peyronie's Disease (GAPD) questionnaire was completed at week 7. No patients received previous local treatment for PD and all had at least 1 year stable disease. IIHA were performed every other week under penile block of 15 mL plain mepivacaine 1% for total number of 3 injections in six weeks; investigator modelling has been fulfilled at the end of each injection. Patients were educated to home modeling, stretching and using daily vacuum device between injections. The median penile curvature at baseline was 55 (IQR= 43.75 - 65). Of the treated patients 16 (88%) showed a decrease in the angle of curvature by a mean of 13.33 ± 8.57 degrees. At 7 weeks the median measured curvature was 40 (IQR = 30 – 50) (p<0.001). A statistically significant improvement in IIEF- Intercourse Satisfaction (from 30,1 ± 7.1 to 34.7 ± 8.1; p<0.001). Hyaluronic acid injections were well tolerated by all patients and no complications were observed. Our preliminary study showed that IIHA may reduce penile curvature in patients affected by Peyronie's Disease in combination with the use of vacuum device, penile modelling and stretching. Considering the safety, the low cost and efficacy, we believe that IIHA may be a promising treatment option. The authors reported no conflict of interest.