Injection Of Prostaglandin E2 Research Articles

Accuracy of MRI without intracavernosal prostaglandin E1 injection in staging, preoperative evaluation, and operative planning of penile cancer.

To evaluate the performance of non-erectile MRI in staging and preoperative evaluation of penile carcinomas, compared to postoperative histopathology. In this retrospective study, MRI scansof patients who had undergone surgery for penile carcinoma (n = 54) between January 2012 and April 2018 were read by two radiologists; anddisagreement was solved in the presence of a third experienced radiologist. Data necessary for preoperative evaluation and staging were collected and compared with final postoperative histology and the type ofsurgery performed. All MRI had been performed without intracavernosal injection of prostaglandin E1 and with IV Gadolinium, as per local protocol. 54 patients were included in the study (mean age 57.52 ± 12.78). The number of patients with T1, T2, and T3 staging in histopathology were 32, 14, and 8. Moderate interobserver agreement was found for staging, disease-free penile length, and all subsites except urethra, which had weak agreement. Strong agreement of consensus MRI with final histopathological staging was found (49/54, weighted κ = 0.85), with high sensitivity and specificity. Sensitivity and specificity for involvement of corpus spongiosum, corpora cavernosa, and urethra were 95.5% and 93.8%, 87.5% and 97.8%, and 90.9% and 86.1%, respectively. Sensitivity (89.6%) and specificity (100%) of MRI for predicting adequate disease-free penile length were high. There were acceptable interobserver agreement and good diagnostic performance of MRI for staging and preoperative assessment without intracavernosal injection, especially for higher stages and higher degrees of invasion which require more extensive surgery.

The analgesic effects of ulinastatin either as a single agent or in combination with sufentanil: A novel therapeutic potential for postoperative pain

Ulinastatin is a broad-spectrum protease inhibitor widely used for the treatment of various inflammation-related diseases owing to its recognized excellent anti-inflammatory and cytoprotective properties. However, whether ulinastatin can relieve postoperative pain remains unclear. In this study, we evaluated the analgesic effects of ulinastatin administered either as a single agent or in combination with sufentanil in a validated preclinical rat model of postoperative pain induced by plantar incision. We found that incisional surgery on the hind paw of these rats induced sustained ipsilateral mechanical pain hypersensitivity that lasted for at least 10 days. A single intraperitoneal (i.p.) injection of ulinastatin prevented the development and reversed the maintenance of incision-induced mechanical pain hypersensitivity in a dose-dependent manner. However, ulinastatin had no effect on the baseline nociceptive threshold. Moreover, repeated i.p. injections of ulinastatin persistently attenuated incision-induced mechanical pain hypersensitivity and promoted recovery from the surgery. The rats did not develop any analgesic tolerance over the course of repeated injections of ulinastatin. A single i.p. injection of ulinastatin was also sufficient to inhibit the initiation and maintenance of incision-induced hyperalgesic priming when the rats were subsequently challenged with an ipsilateral intraplantar prostaglandin E2 injection. Furthermore, the combined administration of ulinastatin and sufentanil significantly enhanced the analgesic effect of sufentanil on postoperative pain, which involved mechanisms other than a direct influence on opioid receptors. These findings demonstrated that ulinastatin had a significant analgesic effect on postoperative pain and might be a novel pharmacotherapeutic agent for managing postoperative pain either alone or as an adjuvant.

Prostaglandin E2-induced anorexia involves hypothalamic brain-derived neurotrophic factor and ghrelin in chicks

Central administration of prostaglandin E2 (PGE2) is associated with potent anorexia in rodents and chicks, although hypothalamic mechanisms are not fully understood. The objective of the present study was to identify hypothalamic nuclei and appetite-related factors that are involved in this anorexigenic effect, using chickens as a model. Intracerebroventricular injection of 2.5, 5, and 10 nmol of PGE2 suppressed food and water intake in broiler chicks in a dose-dependent manner. c-Fos immunoreactivity was increased in the paraventricular nucleus (PVN) at 60 min post injection of 5 nmol of PGE2. Under the same treatment condition, hypothalamic expression of melanocortin receptor 3 and ghrelin mRNAs increased, whereas neuropeptide Y receptor sub-type 5 and tropomyosin receptor kinase B (TrkB) mRNAs decreased in PGE2-treated chicks. In the PVN, chicks injected with PGE2 had more brain-derived neurotrophic factor (BDNF), ghrelin, and c-Fos mRNA but less corticotrophin-releasing factor receptor 1 (CRFR1), CRFR2, and TrkB mRNA expression. In conclusion, PGE2 injection resulted in decreased food and water intake that likely involves BDNF and ghrelin originating in the PVN. Because the anorexigenic effect is so potent and hypothalamic mechanisms are similar in chickens and rodents, a greater understanding of the role of PGE2 in acute appetite regulation may have implications for treating eating and metabolic disorders in humans.

Change in prostaglandin signaling during sickness syndrome hyperalgesia after ovariectomy in female rats

The present study investigated hyperalgesia during sickness syndrome in female rats. Hyperalgesia was induced by an intraperitoneal injection of lipopolysaccharide (LPS) or an intracerebroventricular injection of prostaglandin E2 (PGE2). No differences were found in basal mechanical and thermal thresholds or in LPS-induced hyperalgesia in sham-operated animals in the diestrus or proestrus phase or in ovariectomized (OVX) animals. However, higher levels of PGE2 where found in the cerebrospinal fluid of OVX animals compared to sham-operated females. Intracerebroventricular injection of PGE2 produced rapid mechanical hyperalgesia in sham-operated rats while these responses were observed at later times in OVX animals. The protein kinase A (PKA) inhibitor H-89 reduced mechanical PGE2-induced hyperalgesia in OVX female rats, whereas no effect was observed in sham-operated animals. In contrast, the exchange protein activated by cyclic adenosine monophosphate (cAMP; Epac) inhibitor ESI-09 reduced mechanical PGE2-induced hyperalgesia, whereas no effect was observed in OVX animals. PGE2 also induced thermal hyperalgesia in sham-operated and OVX female rats and a similar effect of ESI-09 was observed. These results suggest that PGE2-induced hyperalgesia that is observed during sickness syndrome has different signaling mechanisms in cycling and OVX female rats involving the activation of the cAMP-Epac or cAMP-PKA pathways, respectively.

Characterization of acute pain-induced behavioral passivity in mice: Insights from statistical modeling.

Affective-motivational disturbances are highly inconsistent in animal pain models. The reproducibility of the open-field test in assessing anxiety, malaise or disability remains controversial despite its popularity. While traumatic, persistent or multiregional pain models are commonly considered more effective in inducing negative affect or functional impairment, the early psychobehavioral changes before pain chronification are often underexplored. Here, we aimed to clarify the fundamental relationship between hypernociception and passive distress-like behavior using a model of transient inflammatory pain. To minimize latent confounders and increase data consistency, male C57BL/6N mice were habituated to the open-field arena 6 times before receiving the unilateral intraplantar injection of prostaglandin E2 (PGE2) or vehicle. Open-field (40-min exploration) and nociceptive behavior were evaluated repeatedly along the course of hypernociception in both wild-type and transgenic mice with a known pronociceptive phenotype. To reduce subjectivity, multivariate open-field behavioral outcomes were analyzed by statistical modeling based on exploratory factor analyses, which yielded a 2-factor solution. Within 3hr after PGE2 injection, mice developed significantly reduced center exploration (factor 1) and a marginally significant increase in their habituation tendency (factor 2), which were not apparent in vehicle-injected mice. The behavioral passivity generally improved as hypernociception subsided. Therefore, transient inflammatory irritation is sufficient to suppress mouse open-field exploratory activity. The apparent absence of late affective-motivational changes in some rodents with prolonged hypernociception may not imply a lack of preceding or underlying neuropsychological alterations. Procedural pain after invasive animal experiments, however small, should be assessed and adequately controlled as a potential research confounder.

Osteocytic Connexin43 Channels Regulate Bone-Muscle Crosstalk.

Bone–muscle crosstalk plays an important role in skeletal biomechanical function, the progression of numerous pathological conditions, and the modulation of local and distant cellular environments. Previous work has revealed that the deletion of connexin (Cx) 43 in osteoblasts, and consequently, osteocytes, indirectly compromises skeletal muscle formation and function. However, the respective roles of Cx43-formed gap junction channels (GJs) and hemichannels (HCs) in the bone–muscle crosstalk are poorly understood. To this end, we used two Cx43 osteocyte-specific transgenic mouse models expressing dominant negative mutants, Δ130–136 (GJs and HCs functions are inhibited), and R76W (only GJs function is blocked), to determine the effect of these two types of Cx43 channels on neighboring skeletal muscle. Blockage of osteocyte Cx43 GJs and HCs in Δ130–136 mice decreased fast-twitch muscle mass with reduced muscle protein synthesis and increased muscle protein degradation. Both R76W and Δ130–136 mice exhibited decreased muscle contractile force accompanied by a fast-to-slow fiber transition in typically fast-twitch muscles. In vitro results further showed that myotube formation of C2C12 myoblasts was inhibited after treatment with the primary osteocyte conditioned media (PO CM) from R76W and Δ130–136 mice. Additionally, prostaglandin E2 (PGE2) level was significantly reduced in both the circulation and PO CM of the transgenic mice. Interestingly, the injection of PGE2 to the transgenic mice rescued fast-twitch muscle mass and function; however, this had little effect on protein synthesis and degradation. These findings indicate a channel-specific response: inhibition of osteocytic Cx43 HCs decreases fast-twitch skeletal muscle mass alongside reduced protein synthesis and increased protein degradation. In contrast, blockage of Cx43 GJs results in decreased fast-twitch skeletal muscle contractile force and myogenesis, with PGE2 partially accounting for the measured differences.

Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation.

Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 μg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 μg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 μg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 μg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 μg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 μg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.

Effect of Intracavernosal Injection of Prostaglandin E1 on Duration and Rigidity of Erection in Patients With Vasculogenic Erectile Dysfunction: Is It Dose Dependent?

ObjectiveTo assess if the effect of intracavernosal injection of prostaglandin E1 (PGE1) on duration and rigidity of erection is dose dependent in patients with different types of vasculogenic erectile dysfunction (ED)? MethodsA hundred patients with ED were assigned into 4 groups (n = 25/each); group (A) patients with arteriogenic ED, group (B) patients with veno-occlusive ED, group (C) patients with mixed (arteriogenic and veno-occlusive) ED, and group (D) patients who have only psychogenic ED (control). After intracavernosal injection of PGE1, patients were assessed using penile Doppler ultrasonography and erection hardness score together with calculation of erection duration. The starting dose of PGE1 was 5 μg which was increased to 10 µg and 20 µg as a maximal dose when needed. ResultsThe mean PSV of patients in groups A, B, C, and D were 24.38 ± 3.3, 37.74 ± 8.28, 22.24 ± 3.85, and 47.76 ± 6.27, respectively. In group D, 88% have achieved the best response at dose of 5 µg while 5.3%, 21.7%, and 0% have achieved the best response at dose of 5 µg in groups A, B, and C, respectively (P < .05 for each). The rest of patients have required either 10 or 20µg to achieve the best response. Patients in group C have required the highest dose of PGE1 to achieve the best response (P < .05). ConclusionIntracavernosal injection of PGE1 in escalating doses have improved the rigidity and duration of erection in patients with different types of vasculogenic ED. Patients with mixed arteriogenic and veno-occlusive ED have required the highest dose of PGE1 to achieve the best response.

Prostaglandin E2 breaks down pericyte\u2013endothelial cell interaction via EP1 and EP4-dependent downregulation of pericyte N-cadherin, connexin-43, and R-Ras

A close association between pericytes and endothelial cells (ECs) is crucial to the stability and function of capillary blood vessels and microvessels. The loss or dysfunction of pericytes results in significant disruption of these blood vessels as observed in pathological conditions, including cancer, diabetes, stroke, and Alzheimer’s disease. Prostaglandin E2 (PGE2) is a lipid mediator of inflammation, and its tissue concentration is elevated in cancer and neurological disorders. Here, we show that the exposure to PGE2 switches pericytes to a fast-migrating, loosely adhered phenotype that fails to intimately interact with ECs. N-cadherin and connexin-43 in adherens junction and gap junction between pericytes and ECs are downregulated by EP-4 and EP-1-dependent mechanisms, leading to breakdown of the pericyte–EC interaction. Furthermore, R-Ras, a small GTPase important for vascular normalization and vessel stability, is transcriptionally repressed by PGE2 in an EP4-dependent manner. Mouse dermal capillary vessels lose pericyte coverage substantially upon PGE2 injection into the skin. Our results suggest that EP-mediated direct disruption of pericytes by PGE2 is a key process for vascular destabilization. Restoring pericyte–EC interaction using inhibitors of PGE2 signaling may offer a therapeutic strategy in cancer and neurological disorders, in which pericyte dysfunction contributes to the disease progression.

Electroacupuncture Regulates Pain Transition by Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia.

BackgroundAcute pain can transition to chronic pain, presenting a major clinical challenge. Electroacupuncture (EA) can partly prevent the transition from acute to chronic pain. However, little is known about the mechanisms underlying the effect of EA. This study investigated the effect of EA on pain transition and the activation of metabotropic glutamate receptor 5 (mGluR5)–protein kinase C epsilon (PKCε) signaling pathway in the dorsal root ganglia (DRG).MethodsThe hyperalgesic priming model was established by the sequential intraplantar injection of carrageenan (1%, 100 μL) and prostaglandin E2 (PGE2) into the left hind paw of rats. EA treatment (2/100 Hz, 30 min, once/day) was applied at bilateral Zusanli (ST36) and Kunlun (BL60) acupoints in rats. Von Frey filaments were used to investigate the mechanical withdrawal threshold (MWT) at different time points. The protein expression levels of mGluR5 and PKCε in the ipsilateral L4-L6 DRGs of rats were detected by Western blot. Some pharmacological experiments were performed to evaluate the relationship between mGluR5, PKCε and the MWT. It was also used to test the effects of EA on the expression levels of mGluR5 and PKCε and changes in the MWT.ResultsSequential injection of carrageenan and PGE2 significantly decreased the MWT of rats and up-regulated the expression level of mGluR5 and PKCε in the ipsilateral L4-L6 DRGs. EA can reverse the hyperalgesic priming induced by sequential injection of carrageenan/PGE and down-regulate the protein expression of mGluR5 and PKCε. Glutamate injection instead of PGE2 can mimic the hyperalgesic priming model. Pharmacological blocking of mGluR5 with specific antagonist MTEP can prevent the hyperalgesic priming and inhibit the activation of PKCε in DRGs. Furthermore, EA also produced analgesic effect on the hyperalgesic priming rats induced by carrageenan/mGluR5 injection and inhibited the high expression of PKCε. Sham EA produced none analgesic and regulatory effect.ConclusionEA can regulate pain transition and it may relate with its inhibitory effect on the activation of mGluR5-PKCε signaling pathway in the DRGs.

HP-1-4 Filtrated Bone Marrow-Derived Mesenchymal Stem Cell Lysate Improves Erectile Function in a Rat Model of Cavernous Nerve Injury

Oral phosphodiesterase-5 (PDE5) inhibitors and intracavernous injection of prostaglandin E1 (PGE1) are treatments of choice for post radical prostatectomy (RP) erectile dysfunction (ED). However, these treatments are not necessarily effective and the development of a novel and effective therapy for post RP ED is required. Recently, it was reported that mesenchymal stem cell (MSC) transplantation induces nerve regeneration and improves erectile function in a rat model of bilateral cavernous nerve injury (BCNI). However, unexpected differentiation of the transplanted stem cells is still an issue with this approach. To avert this problem, we explored the suitability of filtrated stem cell lysate (FSCL), which contains secreted factors but does not contain MSCs. In this study, we investigated the effects of FSCL on erectile function in a rat model of BCNI. Eight-week-old male Wistar/ST rats underwent BCNI or sham surgery. After surgery, filtrated adipose-derived stem cell lysate (FADSCL) or filtrated bone marrow-derived stem cell lysate (FBMSCL) was injected into the corpus cavernosum. After 4 weeks, erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure under stimulation of the cavernous nerve. Proteomic analysis was performed to identify effective factors in FSCL.

Time-effect of penile color duplex Doppler ultrasound for diagnosing vascular erectile dysfunction.

This study aimed to explore the time-effect of color duplex Doppler ultrasound (CDDU) in the diagnosis of vascular erectile dysfunction (ED). Using a self-control study, we included patients who underwent penile CDDU and cavernosography in our hospital. We compared the arterial peak systolic velocity (PSV) of CDDU among different intervals for the diagnosis of arterial ED. We included 357 patients who were under consideration for vascular ED. We found significant differences in all the pairwise comparison of PSV in the 1st (0-5 min), 2nd (6-10 min), 3rd (11-15 min), and 4th (16-20 min) 4 intervals after the injection of prostaglandin E1 (p<0.001), except the 11-15 min vs. the 16-20 min interval (p=0.387). Using cavernosography, 294 patients were diagnosed with venous ED. Compared with other intervals, the diagnosis of CDDU 11-15 min after the intracavernous injection of 20 ug prostaglandin E1 (PGE1) had the best consistency with cavernosography (Kappa=0.761; p<0.001). Compared with other intervals, CDDU at 11-15 min had the highest specificity (93.65%), the highest Youden index (0.85), positive likelihood ratio of 14.46, positive predictive value of 98.54%, negative predictive value of 71.08% and a coincidence rate of 92.16%. Our findings support the increased utilization of CDDU for the diagnosis of both arterial and venous ED. The diagnosis at 11-15 min after intracavernous injection of PGE1 is accurate and stable, which would help to simplify the process and shorten the time of CDDU.

Preventing the need for revision surgery after penile plication reconstruction of Peyronie's deformities.

The need for repeat penile plication (PP) for persistent penile deformity has previously been associated with (I) poor initial erectile response to intracavernosal injection (ICI), (II) an inadequate number of corrective sutures, and (III) a lack of sutures along the proximal shaft of the penis. We present our current experience with PP after implementing corrective measures to assess whether our need for revision surgery was reduced. We performed a retrospective review of patients who underwent PP for Peyronie's disease (PD) between 2009-2018 and had a minimum follow-up of 6 months. We updated our surgical technique in 2016 by (I) using supplemental intracorporal saline injections if the initial erection response to prostaglandin E1 injection was inadequate, (II) increasing numbers of corrective plication sutures, and (III) emphasizing more proximal suture placement. Patients were stratified into two groups and outcomes compared (prior technique versus current technique). Of 472 PP patients who met inclusion criteria, 340 (72%) plication patients before 2016 were compared to 132 (28%) performed after 2016. The revision rate in the current cohort (1.5%, 2/132) decreased by more than half compared to the previous cohort (3.8%, 13/340). Mean preoperative angle of curvature was similar between the two groups (50.4 vs. 51.4 degrees, P=0.64), while the average residual postoperative degree was smaller in the current group (7.36 vs. 2.14 degrees, P<0.001). Fewer sutures were used in the early cohort than in the current (7.63 vs. 8.38, P=0.04). After revision, all cases were functionally straight, with a mean postoperative curvature of 4 degrees at a median follow-up of 10.6 months (IQR, 2.08-20.7). Ensuring adequate rigidity with additional ICI and focusing a greater number of corrective sutures in a more proximal location appears to help prevent the need for revision plication surgery.

Prostaglandin E1 effects on CD62p and PAC-1 in patients with sudden sensorineural hearing loss

PerspectivesTo evaluate the treatment outcome of vasodilator prostaglandin E1 (PGE1) in treating sudden sensorineural hearing loss (SSNHL) and to determine its effects on platelet activation, as reflected by changes in CD62p and PAC-1. MethodsWe prospectively enrolled 60 patients with confirmed SSNHL and randomly divided them into two groups: the SSNHL group received regular therapy, and the SSNHL-PGE1 group received additional intravenous injection of PGE1. After 14 days of treatment, we measured clinical improvement and CD62p-positive and PAC-1-positive platelets. 30 healthy medical staff members were included as a control group. ResultsThe SSNHL patients had significantly higher levels of CD62p-positive or PAC-1 positive platelets than the healthy subjects. The ratios of CD62p positive or PAC-1 positive platelets significantly decreased after the two treatments. The average pure tone (PTA) hearing thresholds decreased to 26.51 ± 12.65 dB in SSNHL-PGE1 group after treatment, which was significantly lower than that of the SSNHL group (34.46 ± 10.35 dB). Patients with initial severe or profound hearing loss (PTA ≥ 71 dB) had better hearing improvement on PGE1 than on the regular treatment. Patients in the SSNHL-PGE1 treatment group had significantly lower CD62p and PAC-1 levels than those in the SSNHL group. Patients with higher initial positive CD62p and PAC-1 ratios tended to have higher potential of clinical improvement and hearing gains after PGE1 treatment. Initial CD62p and PAC-1 levels were significantly correlated with hearing thresholds in patients with SSNHL. ConclusionPGE1 application could improve treatment efficacy and suppress excessive platelet activation in patients with SSNHL.

α2-Adrenoceptor agonist induces peripheral antinociception via the endocannabinoid system.

Xylazine is an α2 adrenoceptor agonist that is extensively used in veterinary medicine and animal experimentation procedures to produce analgesia, sedation and muscle relaxation without causing general anesthesia. Considering the lack of knowledge of the mechanisms involved in peripheral antinociception induced by xylazine and the potential interactions between the adrenergic and endocannabinoid systems, the present study investigated the contribution of the latter system in the mechanism of xylazine. The rat paw pressure test, in which hyperalgesia was induced by the intraplantar injection of prostaglandin E2, was performed. Xylazine administered via an intraplantar injection (25, 50 and 100μg) induced a peripheral antinociceptive effect against prostaglandin E2 (2μg)-induced hyperalgesia. This effect was blocked by treatment with the selective CB1 cannabinoid antagonist AM251 (20, 40 and 80μg) but not by the selective CB2 cannabinoid antagonist AM630 (100μg). The anandamide reuptake inhibitor VDM11 (2.5μg) intensified the peripheral antinociceptive effect of a submaximal dose of xylazine (25μg), and the inhibitor of endocannabinoid enzymatic hydrolysis, MAFP (0.5μg), showed a tendency towards this same effect. In addition, liquid-chromatography mass spectrometric analysis indicated that xylazine (100μg) treatment was associated with an increase in anandamide levels in the rat paws treated with PGE2. The present results provides evidence that the peripheral antinociceptive effect of the α2 adrenoceptor agonist xylazine probably results from anandamide release and subsequent CB1 cannabinoid receptor activation.

367 Intracavernous Injection of PGE1 and Couple Collaborative Treatment for PDE5i-resistant Psychogenic ED

To explore the therapeutic effects of intracavernous injection of PGE1 (prostaglandin E1) and couple collaborative treatment for PDE5i-resistant Psychogenic ED. Twenty-seven PDE5i-resistant Psychogenic ED patients were treated and observed with a duration of 8 weeks. All patients had no sexual experiences, and were unable to intercourse after receiving at least 4 times of on-demand adequate dose of PDE5i. In all cases, the night tumescence of all patients measured by Rigiscan Plus was physiological, and the arterial flow >30cm/s measured by ICI+CDDU. The matters need attention and procedures of ICI were told by the physician. The wife and sexual partner of twelve patients was educated and explained the inductive of Psychogenic ED, and how to cooperate to fulfill intercourse (Group A). Meanwhile, the wife of rest 15 patients was unwilling to undertake couple collaborative treatment. Patients received ICI of 10 μg of PGE1 15 min before sexual demand, and then fulfilled intercourse. Patients reported their degree of satisfaction of sexual behavior next day and received encouraging psychological suggestion.

Hippocampus and dentate gyrus morphological сhanges in posterity of female rats after receiving PgE2 for labor induction.

Background. The effect of labor stimulation on the brain structure still remains an unexplored issue. Objective. To determine the morphological hippocampus and dentate gyrus changes in laboratory rats on the first day of life after intravaginal injection of prostaglandin E2 for labor induction. Methods. The changes in the structure of hippocampus and dentate gyrus in posterity of white syngenic rats on the first day of life have been studied. Pregnant females of the experimental group were injected PgE2 in the form of a gel intravaginally to stimulate labor on the 22th day of pregnancy. The duration of the experimental rats pregnancy amounted to 23 day, in the intact group - 23-24 day after conceiving. The cerebral hemisphere was fixed in a 10% neutral formalindegid solution, dehydrated in an ascending battery of ethyl spirits. 5 μm paraffin sections were stained with hematoxylin and eosin. The thickness of the layers of hippocampus and dentate gyrus, the number of cells of the granular and pyramidal layers per unit area and their sizes, the area of the neurons nuclei of hippocampus and dentate gyrus were determined in the histological samples. Results. Hippocampus and dentate gyrus in posterity of female rats after receiving PgE2 for labor induction is characterized by a thinning of the pyramidal and granular layers, a decrease in the area of the neurons nuclei, and a decrease in the perimeter of the neurons pericarion neurons in all the studied zones. The decrease in the number of cells is determined only in the dentate gyrus. Conclusion. 1. On the 1st day of life in posterity of female rats after receiving PgE2 for for labor induction there is a tendency to thinning of the pyramidal layer of CA1, CA2 and CA3 fields of hippocampus in combination with a decrease of neurons size of the CA1 field of hippocampus in the experimental group compared to the intact one. 2. In experimental rats there is a decrease of the area of neurons nuclei in the regions CA1, CA2, CA3 and the dentate gyrus compared with the control group. 3. The morphological changes of the hippocampus and dentate gyrus in posterity of female rats after receiving PgE2 for labor induction correspond to the brain changes after experimental fetal hypoxia.

P6261Aortic stiffness and carotid intima thickness in hypercholesterolemic males with erectile dysfunction: relation to smoking status and statin therapy

Abstract Purpose Aim of the study was to examine possible differentiation of aortic stiffness and carotid atherosclerosis among hypercholesterolemic patients with erectile dysfunction (ED) according to smoking status and statin therapy. Methods We measured carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cfPWV) in three age-matched groups of ED patients with a moderate cardiovascular risk (SCORE) and low-density lipoprotein cholesterol (LDL-C) level greater than or equal to 100 mg/dL: Smokers not receiving statin therapy (n=106), Smokers actively under statin treatment for at least three months with no dose adjustment for a minimum of six weeks (n=59) and Non-smokers not receiving statin therapy (n=97). The severity of ED was evaluated with measurements of penile peak velocity (PSV) 20 min after the intracavernous injection of prostaglandin E1 (20 μg). Results The groups of untreated smokers and non-smokers had similar mean LDL-C level. The mean LDL-C of patients under statin therapy was lower, however the differences with the level of the untreated patients was not statistically significant. Overall 33 (56%) of the patients under statin therapy reached their LDL-C goal. Body mass index and the prevalence of hypertension were not different between the three groups. The PSV was significantly lower in smokers with or without therapy compared to that of non-smokers, denoting significant influence of smoking status on the smaller in size penile arteries and consequently, a unfavorable effect on erectile function. Figure illustrates the differences in cfPWV (left plot) and cIMT (right plot) mean (±SE) values between the three groups. Smokers not receiving statin therapy had significantly higher cfPWV compared to the other groups while smokers under statin therapy had no different cfPWV than that of non-smokers not receiving therapy. The cIMT values were not different between the three groups. Smoking, statins and vascular changes Conclusions Smokers ED patients receiving statin therapy exhibited similar atherosclerotic burden compared to untreated hypercholesterolemic individuals, however, the cfPWV was significantly lower, possibly because of the known pleiotropic effects of these drugs on the aortic elastic properties. Although the cross-sectional design precludes drawing conclusions of causal relationships, the findings of this study have important clinical implications given the harmful effect of both hypercholesterolemia and smoking in men suffering from ED and the higher risk for future cardiovascular events that ED confers.

P806High normal blood pressure and vascular parameters in patients with erectile dysfunction

Abstract Purpose High blood pressure (BP) is a common risk factor for erectile dysfunction (ED) which is considered as an early clinical manifestation of generalized vascular disease. High–normal BP (130–139/85–89 mmHg) is associated with high rates of progression to hypertension. Aim of the study is to examine vascular and structure parameters of patients with high-normal BP complaining of ED. Methods We assessed macrovascular and microvascular (penile vascular damage) changes in four age-matched groups without a history of diabetes and cardiovascular disease; Normal BP (n=162), high-normal BP (n=87), stage I hypertension (n=49) and stage II and III hypertension (n=44). All hypertensive patients were not receiving antihypertensive therapy. Indices of vascular function and structure including carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), carotid intima media thickness (cIMT) and microvascular damage (penile vasculature) were evaluated in all patients. 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 Body-mass index (BMI) was significantly higher in patients with hypertension and patients with high- normal BP compared to subjects with normal BP. Smoking prevalence and LDL-C level were not different between the four subgroups. Figure shows a progressive increase in PWV and cIMT from normal BP group, to patients with high- normal BP and to untreated patients with hypertension. Compared to patients with normal BP, patients with high- normal BP had significantly higher PWV (p&lt;0.01), cIMT (p&lt;0.05), AIx (p&lt;0.05) and lower penile PSV (p&lt;0.01). Interestingly, figure shows that the individuals with high- normal BP level and patients with stage I hypertension had similar AIx and penile PSV denoting no difference in central haemodynamics and penile vasculature between the two groups. High-normal BP and vascular parameters Conclusions Middle-aged men with high-normal BP have significant microvascular and macrovascular damage compared to subjects with normal BP. The ultrasonographically documented functional changes in the vascular wall of the smaller in size penile vasculature are similar to that of men with stage I arterial hypertension. These findings bring new insights into the clinical significance of high- normal BP, which might be a premising therapeutic target for men with ED who are considered to be at a higher cardiovascular risk.

Does medication administration affect the rate of orthodontic tooth movement and root resorption development in humans? A systematic review.

Recently, the potential impact of different medications on the rate of orthodontic tooth movement and the associated root resorption has been systematically reviewed in animal studies and various effects have been shown. However, animal data cannot be extrapolated to human clinical situations directly. To systematically investigate the most up to date available evidence from controlled human studies regarding the effect of medication administration on the rate of orthodontic tooth movement and associated root resorption development. We searched eight databases (covering also grey literature) without restrictions and we performed hand searching up until October 2018. Controlled studies in humans assessing the effect of various medications on the rate of orthodontic tooth movement and root resorption development. Study selection was followed by data extraction and risk of bias assessment using the ROBINS-I tool for non-randomized and the Cochrane Risk of Bias Tool for randomized studies. Eight studies, at various risk of bias, were finally identified. With regard to the rate of orthodontic tooth movement, local injections of prostaglandin E1 were found to exert an increasing effect, whereas systemic intake of nabumetone decreased it. Following tenoxicam administration, drinking water with fluoride or local injections of calcitriol (vitamin D metabolite), no significant effects were demonstrated. Concerning root resorption development, nabumetone administration was shown to reduce it, whereas fluoride, overall, was not observed to exert any effect. Only in individuals subjected to heavy orthodontic forces, did fluoride show a protective effect for the period of force application, but not in the longer term during retention. The aforementioned substances may show varying effects on the rate of orthodontic tooth movement and root resorption development in human subjects. Despite the observed limitations, the orthodontist should be able to identify patients taking pharmaceuticals and consider any implications related to orthodontic treatment. PROSPERO (CRD42017078208).