Stereological comparison of smooth muscle, collagen, and elastic fibers of the clitoris and glans penis in young adults.

OBJECTIVE: To compare the collagen, elastic fibers, and smooth muscle content of the clitoris and the glans penis in young adults. MATERIALS AND METHODS: The clitoris and the glans penis of six women and six men (mean age 25±3) who died as a result of accidents were excised. The samples were placed under a formaldehyde solution and histologically processed. Masson's trichrome and Weigert's resorcin-fuchsin stain was used to highlight the elastic fibers, smooth muscle, and collagen. Stereological analysis was conducted in 5 random fields of 5 slides for each sample. For statistical analysis, the unpaired t-test was used to compare values between groups, and a value of P<0.05 was considered as significant for all analyses. RESULTS: Stereology revealed a mean smooth muscle content of 35.84±6.46% and 31.64±4.74% for the clitoris and glans penis, respectively, while it also revealed collagen content of 26.11±7.41% and 28.44±3.55% and elastic fibers content of 24.12±4.34% and 30.97±6.13% for the clitoris and glans penis, respectively. The statistical analysis showed no significant differences between them. CONCLUSION: Regardless of anatomical differences, the volumetric density of collagen, elastic fibers, and smooth muscle were similar for the clitoris and glans penis in young adults, a feature possibly explained by their embryology.

Proteomic and Clinicopathologic Assessment of Penile Amyloidosis: A Single Institutional Review of 12 Cases.

OBJECTIVES: There is a paucity of data on penile amyloidosis. We aimed to assess the frequency of different amyloid types in surgical specimens from the penis involved by amyloidosis and correlate relevant clinicopathologic parameters with proteomic findings. METHODS: Since 2008, our reference laboratory has performed liquid chromatography/tandem mass spectrometry (LC-MS/MS) for amyloid typing. The institutional pathology archive and reference laboratory database were queried to retrospectively identify all penile surgical pathology specimens with LC-MS/MS results between January 1, 2008, and November 23, 2022. Archived H&E-stained and Congo red-stained sections were re-reviewed. RESULTS: Twelve cases of penile amyloidosis were identified, which represented 0.35% (n = 3,456) of penile surgical specimens. AL-type amyloid was most frequent (n = 7), followed by keratin-type amyloid (n = 3) and ATTR (transthyretin)-type amyloid (n = 2). AL-type amyloid cases often showed diffuse dermal/lamina propria deposition, whereas all keratin-type amyloid cases were localized to the superficial dermis. Two cases with keratin-type amyloid had concomitant cutaneous findings (penile intraepithelial neoplasia and condyloma). CONCLUSIONS: This series, the largest to date, demonstrates that penile amyloidosis has a heterogeneous proteomic landscape. To the best of our knowledge, this is the first study describing ATTR (transthyretin)-type penile amyloid.

A Bioinformatic Investigation of the Mechanism Underlying Migraine-Induced Erectile Dysfunction.

BACKGROUND: Over recent years, an increasing body of literature has focused on the relationship between erectile dysfunction (ED) and migraine. However, the specific mechanism is unclear. MATERIALS AND METHODS: We used a bioinformatic database to predict the targets and pathways associated with migraine and ED. Twenty male SD rats were randomly divided into a blank group (Group A, n = 10) and a migraine model group (Group B, n = 10). The rats in Group A were subcutaneously injected with normal saline (2 ml/kg) into the back of the neck. Rats in Group B were subcutaneously injected with nitroglycerin 10 mg/kg (5 mg/ml) into the back of the neck in order to create an animal model of migraine. Next, we carried out the measurement of erectile function. We used hematoxylin and eosin (HE) to compare the tissue structure of the cavernous body of the penis. Western blotting was used to determine the expression levels of PI3K, p-AKT, and p-mTOR in the protein; Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was used to determine the expression levels of PI3K, AKT, and mTOR in the messenger ribonucleic acid (mRNA). RESULTS: There are 117 intersection targets of migraine and ED, involving 188 cell biological processes (BP), 21 cellular components (CC), 31 molecular functions (MF), and 65 signaling pathways. HE staining results show that there were no significant differences between Group A and Group B with regard to any of the parameters. Compared with Group A, the levels of the PI3K, p-AKT, and p-mTOR proteins and PI3K, AKT, and mTOR mRNAs in Group B decreased (P < 0.01). CONCLUSIONS: The decline of erectile function in a rat model of migraine was associated with the PI3K/Akt/mTOR signaling pathway.

Expression of AIF, PARP, and miRNAs MIR-145, MIR-210, and MIR-486 associated with apoptosis in the corpus cavernosum of rats subjected to chronic alcoholism model / Expresión de AIF, PARP y miRNAs MIR-145, MIR-210 y MIR-486 asociados con apoptosis en el cuerpo cavernoso de ratas sometidas a modelo de alcoholismo crónico

SUMMARY: Previous studies from our group described the consequences of using ethanol on penile erection. Nevertheless, the molecular mechanisms surrounding microRNAs, apoptosis process and their relationship with erectile dysfunction associated with alcohol consumption are still poorly understood. The objective of this analysis was to evaluate the mechanism of apoptosis by the expression of AIF and PARP, as well as their regulatory microRNAs: miR-145, miR-210 and miR-486, in the corpus cavernosum of rats submitted to a semivoluntary alcoholism model. For this study 24 Wistar rats were divided into two groups: control (C) and treated with 20 % ethanol (A) for seven weeks. The corpus cavernosum samples were prepared for immunohistochemical analysis of AIF and PARP protein expression, and microRNAs miR-145, miR-210, miR-486 gene expression in cavernous tissue was performed by real time PCR. The immunohistochemical analysis showed little nuclear positive labeling for the protein PARP and AIF in the corpus cavernosum of control and ethanol treated animals. After analysis of miR-145, -210 and -486 microRNA expression in the 12 animals studied, no results were found with significant statistical difference between the control and alcoholized groups. The expression of AIF and PARP and their regulatory microRNAs involved in apoptotic process (miR-145, miR-210 and miR-486) were not altered in the corpus cavernosum of rats submitted to semivoluntary alcoholism.

RESUMEN: Estudios previos de nuestro grupo describieron las consecuencias del uso de etanol en la erección del pene. Sin embargo, los mecanismos moleculares que rodean a los microARN, el proceso de apoptosis y su relación con la disfunción eréctil asociada con el consumo de alcohol aún no se conocen bien. El objetivo de este análisis fue evaluar el mecanismo de apoptosis mediante la expresión de AIF y PARP, así como sus microARN reguladores: miR-145, miR-210 y miR-486, en el cuerpo cavernoso de ratas sometidas a un modelo de alcoholismo semivoluntario. Se dividieron 24 ratas Wistar en dos grupos: control (C) grupo de ratas tratadas con etanol al 20 % (A) durante siete semanas. Las muestras del cuerpo cavernoso se prepararon para el análisis inmunohistoquímico de la expresión de la proteína AIF y PARP, y la expresión del gen microRNAs miR-145, miR-210, miR-486 en tejido cavernoso se realizó por PCR en tiempo real. El análisis inmunohistoquímico mostró escaso etiquetado nuclear positivo para la proteína PARP y AIF en el cuerpo cavernoso de los animales de control y tratados con etanol. Después del análisis de la expresión de microARN miR-145, -210 y -486 no se encontraron resultados con diferencias estadísticas significativas entre los grupos control y alcoholizados. La expresión de AIF y PARP y sus microARN reguladores involucrados en el proceso apoptótico (miR-145, miR-210 y miR-486) no se alteraron en el cuerpo cavernoso de las ratas sometidas a alcoholismo semivoluntario.

Evaluation of effectiveness of antiandrogen treatments on cavernosal tissues in rats.

In this study, we aimed to compare changes in cavernosal tissues in rats with antiandrogen treatment and orchiectomy. A total of 42 Wistar albino rats were divided into four groups. Group I, control group, Group II, LH-RH was given for 1 month, Group III-LH-RH + Bicalutamide was given for 1 month, and Group IV was defined as orchiectomy and followed up for 1 month. Measurements of intracavernosal pressure with different electrical stimuli and pathological findings of smooth muscle collagen in cavernosal tissues were examined. While the cavernosal pressure response in all the different electrical stimuli given in the control group and in all other groups was significantly lower than that in the other groups, it was statistically significant at 7.5 and 10 V (p = .005, p < 0001). According to the pathologic evaluation, the density of tissue collagen increased significantly in the other groups according to the control group. In groups 3 and 4, the density of 4+ collagen was found to be increased according to Groups 1 and 2. In the LH-RH alone group, it appears that there are no 4+ colloid density and less damage. According to these findings, the negative effect of LH-RH treatment on cavernosal tissues appears to be less.

Losartan treatment significantly attenuates the fibrotic changes in the corpus cavernosum of castrated rats.

INTRODUCTION AND OBJECTIVES: The aim of this study is to evaluate the effects of castration and subsequent losartan administration on the fibrosis-related parameters in the corpora cavernosa of castrated rats. MATERIAL AND METHODS: Twenty-four male rats were divided into four equal groups. Group 1:sham surgery plus vehicle (0.9% NaCl) (control:con), group 2:sham surgery plus losartan (con+los), group 3: castration plus vehicle (castration:cast) and group 4:castration plus losartan (cast+los). After four weeks of oral losartan treatment, corporal levels of transforming growth factor-beta (TGF-ß), thrombospondin-1 (TSP-1), alpha-actin, beta-actin and fibronectin were investigated by ELISA kits. Changes in the collagen and smooth muscle content were evaluated by histological analysis with Masson trichrome staining. RESULTS: Initial and post-treatment body weights of rats were similar among groups. Castration significantly increased the expression of TGF-ß, TSP-1 and fibronectin and resulted in a significant decrease in alpha-actin levels in the corpora cavernosa. Administration of losartan reduced the levels of TGF-ß, TSP-1 and fibronectin in castrated rats. Alpha actin levels also increased after losartan treatment. Beta-actin levels were not significantly different among 4 groups. The levels of all markers were similar in group 1 and 2. Rate of fibrosis was significantly higher in castrated rats and treatment with losartan reduced this rate. CONCLUSION: Castration increased the expression of fibrosis-related markers in the corpora cavernosa of rats. Administration of losartan significantly attenuated those changes and exerted an antifibrotic effect.

Effect of p-coumaric acid on the erectogenic enzyme activities and non-protein thiol level in the penile tissue of normal and doxorubicin-induced oxidative stress male rat.

This study investigated effect of p-coumaric acid (PCA) on erectogenic enzyme activity and non-protein thiol level in the penile tissue of normal and doxorubicin (DOX)-induced oxidative stress male rat. Sixty-four (64) adult male rats weighing between 170 and 180 g were used for this work. After 14 days of acclimatisation, the rats were divided into eight groups (n = 8). Rats were orally pre-treated with PCA dose dependently (50 and 100 mg/kg body weight [b.w.t]) and vitamin E (100 mg/kg b.w.t) for 14 days before induction with a single dose of DOX (15 mg/kg b.w.t, via i.p.). The result revealed that arginase, acetylcholinesterase (AChE), angiotensin-I-converting enzyme (ACE), phosphodiesterase-5 (PDE-5), adenosine monophosphohydrolase (AMPdase) activities were significantly (p < 0.05) higher in the DOX-induced rats as against the control, which was significantly p < 0.05) higher when compared to normal rats treated with PCA. PCA also improved non-protein thiol level in the penile tissue of both normal and DOX-induced rats. Hence, this study revealed that PCA is capable of causing inhibitory effects on the activities of enzymes, associated with oxidative stress-induced erectile dysfunction (ED) and could also be used as an aphrodisiac agent in the management/treatment of ED.

Persistence of Polydimethylsiloxane Condom Lubricants.

Polydimethylsiloxane (PDMS) is commonly used to lubricate condoms. The detection of PDMS on swabs from complainants can be used to support an allegation of sexual assault. Previous research has focused on establishing analytical techniques for detecting PDMS. This research examined the persistence of PDMS on the penis, in the vagina, in the mouth, and on skin. The longest PDMS detection times were 20 h on the penis, 35 h in the vagina, and 52 h on skin. PDMS was detected up to 4 h in the mouth if the participant did not eat or drink and up to 9 h if the participant slept. PDMS was not detected in the mouth after eating or drinking. The presence of biological fluids had no detrimental effect on the analysis. Aqueous extraction of swabs for DNA did not remove any significant amount of PDMS; hence, swab remains could be subsequently analyzed for PDMS.

Persistent organic pollutants and penile bone mineral density in East Greenland and Canadian polar bears (Ursus maritimus) during 1996-2015.

Persistent organic pollutants (POPs) are long-range transported to the Arctic via atmospheric and oceanic currents, where they biomagnify to high concentrations in the tissues of apex predators such as polar bears (Ursus maritimus). A major concern of POP exposure is their physiological effects on vital organ-tissues posing a threat to the health and survival of polar bears. Here we examined the relationship between selected POPs and baculum bone mineral density (BMD) in the East Greenland and seven Canadian subpopulations of polar bears. BMD was examined in 471 bacula collected between years 1996-2015 while POP concentrations in adipose tissue were determined in 67-192 of these individuals collected from 1999 to -2015. A geographical comparison showed that baculum BMD was significantly lowest in polar bears from East Greenland (EG) when compared to Gulf of Boothia (GB), Southern Hudson (SH) and Western Hudson (WH) Bay subpopulations (all p < 0.05). The calculation of a T-score osteoporosis index for the EG subpopulation using WH bears as a reference group gave a T-score of -1.44 which indicate risk of osteopenia. Concentrations of ΣPCB74 (polychlorinated biphenyls), ΣDDT3 (dichlorodiphenyltrichloroethanes), p,p'-DDE (dichlorodiphenyldichloroethylene), ΣHCH3 (hexachlorohexane) and α-HCH was significantly highest in EG bears while ΣPBDE (polybrominated diphenyl ethers), BDE-47 and BDE-153 was significantly highest in SH bears (all p < 0.04). Statistical analyses of individual baculum BMD vs. POP concentrations showed that BMD was positively correlated with ΣPCB74, CB-153, HCB (hexachlorobenzene), ΣHCH, ß-HCH, ClBz (chlorobenzene), ΣPBDE and BDE-153 (all p < 0.03). In conclusion, baculum density was significantly lowest in East Greenland polar bears despite the positive statistical correlations of BMD vs. POPs. Other important factors such as nutritional status, body mass and body condition was not available for the statistical modelling. Since on-going environmental changes are known to affect these, future studies need to incorporate nutritional, endocrine and genetic parameters to further understand how POP exposure may disrupt bone homeostasis and affect baculum BMD across polar bear subpopulations.

Modulation of some markers of erectile dysfunction and malonaldehyde levels in isolated rat penile tissue with unripe and ripe plantain peels: identification of the constituents of the plants using HPLC.

CONTEXT: Plantain fruit pulp has been used as a natural remedy to manage erectile dysfunction (ED) in traditional medicine. However, the potency of the peel has not been examined with respect to ED management. OBJECTIVE: This study investigated and compared the inhibitory potential of unripe (UPP) and ripe (RPP) plantain peels on some enzymes associated with ED and Fe2+-induced oxidative stress in albino rat penile homogenate in vitro. MATERIALS AND METHOD: Aqueous extract of the peels was prepared and the effect on phosphodiesterase-5 (PDE-5), arginase, acetylcholinesterase (AChE), angiotensin-I converting enzyme (ACE) and Fe2+-induced malonyladehyde in isolated albino rat penile homogenate were investigated. Phenolic constituents of the peels powder were characterized using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). RESULT: Extract from UPP had higher PDE-5 (IC50 = 3.10 µg/mL), arginase (IC50 = 0.96 µg/mL), AChE (IC50 = 6.30 µg/mL) and ACE (IC50 = 0.41 µg/mL) inhibitory ability compared with RPP (PDE-5, IC50 = 4.33 µg/mL; arginase, IC50 = 1.34 µg/mL; AChE, IC50 = 8.64 µg/mL; ACE, IC50 = 0.63 µg/mL). The extract from UPP also had higher inhibition of Fe2+-induced lipid peroxidation. HPLC-DAD analysis revealed that gallic and caffeic acids, rutin, quercitrin and quercetin were abundant in UPP, while catechin, kaempferol, chlorogenic and ellagic acids were the dominant phenolic compounds in RPP. DISCUSSION AND CONCLUSION: Inhibition of enzymes associated with ED and lipid peroxidation could be linked with the phenolic compounds. However, UPP appeared to be more potent.

Rho/rho-kinase signalling in chronically alcohol-fed mice.

BACKGROUND/AIM: The effects of chronic ethanol consumption on male sexual function are debateable, and its effects on the Rho/Rho-kinase pathway are unknown. Therefore, we investigated smooth muscle reactivity and Rho/Rho-kinase signalling in the corpus cavernosum of ethanol-fed mice. MATERIALS AND METHODS: Ethanol was added to drinking water at 5% concentration in the first 2 days with 5% increment every subsequent 2 days, up to a final concentration of 20% for 45 days. Corpora cavernosa were isolated and a cumulative dose-response curve to phenylephrine was obtained. Acetylcholine (10-6 M), electrical field stimulation (EFS, 40 V, 8-16 Hz) and Y-27632 (10-6-10-5 M)-induced relaxations were compared in the control and ethanol groups. RESULTS: Blood ethanol levels in the control and ethanol-treated mice were 1.5 ± 0.3 mg/dL and 37.4 ± 4.1 mg/dL (P < 0.001), respectively. Phenylephrine-induced contractile responses were potentiated in the ethanol group, with pD2 values of 4.92 ± 0.18 and 5.71 ± 0.21 (P < 0.01) in the corpus cavernosum obtained from control and alcohol-fed mice, respectively. The relaxant responses to acetylcholine and EFS, but not Y-27632, were significantly augmented in the corpus cavernosum obtained from ethanol-treated mice. However, expression and activation of Rho-kinase remained unchanged in the alcohol group. CONCLUSION: Ethanol drinking may increase sensitivity to both vasoconstrictors and vasodilators in the mouse corpus cavernosum without any alteration in Rho/Rho-kinase signalling.

Expression profiles of eNOS, iNOS and microRNA-27b in the corpus cavernosum of rats submitted to chronic alcoholism and Diabetes mellitus.

PURPOSE:: To evaluate the expression of endothelial and inducible NOS in addition to the miRNA-27b in the corpus cavernosum and peripheral blood of healthy rats, diabetic rats, alcoholic rats and rats with both pathologies. METHODS:: Forty eight Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D) and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study protein expressions of eNOS and iNOS by immunohistochemistry and expression of miRNA-27b in the corpus cavernosum and peripheral blood. RESULTS:: Immunohistochemistry for eNOS and iNOS showed an increase in cavernosal smooth muscle cells in the alcoholic, diabetic and alcoholic-diabetic groups when compared with the control group. Similarly, the mRNA levels for eNOS were increased in cavernosal smooth muscle (CSM) in the alcoholic, diabetic and alcoholic-diabetic groups and miRNA-27b were decreased in CSM in the alcoholic, diabetic and alcoholic-diabetic groups. CONCLUSION:: The major new finding of our study was an impairment of relaxation of cavernosal smooth muscle in alcoholic, diabetic, and alcoholic-diabetic rats that involved a decrease in the nitric oxide pathway by endothelium-dependent mechanisms accompanied by a change in the corpus cavernosum contractile sensitivity.

Expression profiles of eNOS, iNOS and microRNA-27b in the corpus cavernosum of rats submitted to chronic alcoholism and Diabetes mellitus

Abstract Purpose: To evaluate the expression of endothelial and inducible NOS in addition to the miRNA-27b in the corpus cavernosum and peripheral blood of healthy rats, diabetic rats, alcoholic rats and rats with both pathologies. Methods: Forty eight Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D) and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study protein expressions of eNOS and iNOS by immunohistochemistry and expression of miRNA-27b in the corpus cavernosum and peripheral blood. Results: Immunohistochemistry for eNOS and iNOS showed an increase in cavernosal smooth muscle cells in the alcoholic, diabetic and alcoholic-diabetic groups when compared with the control group. Similarly, the mRNA levels for eNOS were increased in cavernosal smooth muscle (CSM) in the alcoholic, diabetic and alcoholic-diabetic groups and miRNA-27b were decreased in CSM in the alcoholic, diabetic and alcoholic-diabetic groups. Conclusion: The major new finding of our study was an impairment of relaxation of cavernosal smooth muscle in alcoholic, diabetic, and alcoholic-diabetic rats that involved a decrease in the nitric oxide pathway by endothelium-dependent mechanisms accompanied by a change in the corpus cavernosum contractile sensitivity.

An experimental study: quantitatively evaluating the change of the content of collagen fibres in penis with two-dimensional ShearWave™ Elastography.

The purpose of this study was to explore the value of two-dimensional ShearWave™ Elastography (2D-SWE) on quantitatively evaluating the change of the content of collagen fibres in penis. Twenty male Sprague Dawley rats were divided into the pre-sexual maturity group (Group 1) and the sexual decline group (Group 2) according to age. The ultrafast ultrasound device Aixplorer® (SuperSonic Imagine, Aix-en-Provence, France) was used for 2D-SWE imaging of penis, and the measurement index was shear wave stiffness (SWS). The immunohistochemistry was used to analyse the content of collagen fibres in penis, and the measurement index was positive area percentage (PAP). The differences of SWS between the two groups and PAP between the two groups were analysed. SWS of Group 1 and Group 2 was 10.18 ± 1.09 and 8.02 ± 1.34 kPa, and SWS of Group 2 was significantly lower than Group 1 (p < .01). PAP of Group 1 and Group 2 was 4.83 ± 3.61% and 16.41 ± 10.02%, and PAP of Group 2 was significantly higher than Group 1 (p < .01). Our results indicate that when the content of collagen fibres changes, SWS of penis measured with 2D-SWE would change significantly as well. Two-dimensional SWE can be used to quantitatively evaluate the change of the content of collagen fibres in penis.

Pilot Study Evaluating a Rat Model of Radiation-induced Erectile Dysfunction Using an Image-guided Microirradiator.

OBJECTIVE: To establish a feasible rat model of radiation-induced erectile dysfunction after targeted prostate irradiation using an image-guided irradiation unit specially designed for small-animal radiation research. METHODS: The X-RAD 225Cx research platform was used in the present study. We first performed quality assurance testing using a rat cadaver. After confirming dosimetry, 24 age-matched, young, adult, male rats were assigned to sham radiation or radiation to the prostate with doses of 15, 20, or 25 Gy. To confirm appropriate prostate irradiation, physiological erectile function was evaluated using intracavernous pressure (ICP) measurements with cavernous nerve electrical stimulation at 9 weeks after radiotherapy. Each animal was weighed at the time of ICP measurement. In addition, we investigated the cyclic guanosine monophosphate level in the penile cavernosa using a commercial enzyme-linked immunosorbent assay kit. RESULTS: Quality assurance results confirmed the accuracy of the irradiation technique. Dose-dependent decreases in ICP in irradiated rats were observed without major toxicity. No difference in body weight was noted among the experimental groups. Cyclic guanosine monophosphate levels were significantly decreased in the group that received 25 Gy compared with the age-matched sham-irradiated group. CONCLUSION: High-precision imaging and targeting capabilities provided by the micro-IGRT platform enable us to develop a reproducible animal model of radiation-induced erectile dysfunction in prostate cancer research.

Efficacy of a novel water-soluble curcumin derivative versus sildenafil citrate in mediating erectile function.

The present study was conducted to assess the efficacy of a novel curcumin derivative (NCD) versus sildenafil citrate in erectile signaling. The study was conducted on 10 control male rats and 50 diabetic male rats divided into the following groups: diabetic, curcumin, NCD, sildenafil and NCD combined with sildenafil. Cavernous tissue (CC) gene expression levels of heme oxygenase (HO)-1, Nrf2, NF-κß and p38, enzyme activities of HO and nitric oxide synthase (NOS), cyclic guanosine monophosphate (cGMP) and intracavernosal pressure (ICP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction was confirmed by the significant decrease in ICP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant elevation of NF-κß, p38 genes. Administration of all therapeutic interventions led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1 and Nrf2 gene expression, and a significant decrease in NF-κß, p38 gene expression. NCD or its combination with sildenafil showed significant efficacy and more prolonged duration of action. In conclusion, NCD could enhance erectile function with more efficacy and more prolonged duration of action.

Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction.

The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile signalling was assessed. Ten control male rats and 50 diabetic male rats were used and divided into the following: diabetic (DM), curcumin (CURC), NCD, tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene expression of heme oxygenase-1 (HO-1), Nrf2, NF-B and p38, enzyme activities of heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant increase in NF-Ò ß, p38 genes. Administration of all therapeutic interventions led to a significant increase in ICP/MAP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1, and Nrf2 gene expression, and a significant decrease in NF-Ò ß, p38 gene expression. NCD or its combination with tadalafil showed significant superiority and more prolonged duration of action. In conclusion, a tendency was observed that CURC and NCD have high efficacy and more prolonged duration of action in enhancing erectile function.

Effect of avanafil on rat and human corpus cavernosum.

We compared the activity of a new phosphodiesterase-5 inhibitor (PDE5i) avanafil with sildenafil and tadalafil in human and rat corpus cavernosum (CC) tissues. The effect of avanafil with several inhibitors and electrical field stimulation (EFS) was evaluated on CC after pre-contraction with phenylephrine. With the PDE5i, sildenafil and tadalafil, concentration-response curves were obtained and cyclic guanosine monophosphate (cGMP) levels were measured in tissues. Avanafil induced relaxation with maximum response of 74 ± 5% in human CC. This response was attenuated by NOS inhibitor and soluble guanylate cyclase (sGC) inhibitor. Avanafil potentiated relaxation responses to acetylcholine and EFS in human CC and enhanced SNP-induced relaxation and showed 3-fold increase in cGMP levels. When compared with sildenafil, avanafil and tadalafil were effective at lower concentrations in human CC. In addition, Sprague-Dawley rats underwent in vivo intracavernosal pressure (ICP) and mean arterial pressure (MAP) measurements. Avanafil increased ICP/MAP that was enhanced by SNP and cavernous nerve (CN) stimulation in rat CC tissues. Also avanafil showed maximum relaxation response of 83 ± 7% in rat CC with 3-fold increase in cGMP concentration. Taken together, these results of our in vivo and in vitro studies in human and rat suggest that avanafil promotes the CC relaxation and penile erection via NO-cGMP pathway.

Intracellular calcium concentration of corpus cavernosum smooth muscle cells is decreased by the overexpression of PnNOS gene in adipose tissue-derived stem cells.

The study investigated the effects of adipose tissue-derived stem cells (ADSCs) modified with penile neuronal nitric oxide synthase (PnNOS) gene on intracellular calcium concentration in rat corpus cavernosum smooth muscle cells (CCSMCs). ADSCs and CCSMCs of Sprague-Dawley (SD) rats were isolated and cultured in vitro respectively. The rat PnNOS gene was transferred into the ADSCs mediated by a recombinant adenovirus vector. The expression of the PnNOS gene was detected. At the same time, the concentration of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) was assayed. After coculturing with the CCSMCs of SD rats, which were isolated and expanded ex vivo, the cGMP and NO levels of ADSCs and CCSMCs were measured. Intracellular calcium concentration ([Ca(2+) ]i ) in rat CCSMCs was measured with Fluo-3/AM by flow cytometer after cocultured with ADSCs overexpressing PnNOS gene. The mRNA and protein expression of PnNOS gene mediated by recombinant adenovirus vector significantly overexpressed and lasted at least 2 weeks. Meanwhile, the concentration of NO and cGMP in ADSCs was greatly increased. The concentration of cGMP was significantly increased, and [Ca(2+) ]i was obviously decreased in CCSMCs compared with the control groups (P < 0.05) after cocultured with ADSCs for 3 days. These findings demonstrated that ADSCs overexpressing PnNOS gene might decrease [Ca(2+) ]i in CCSMCs by up-regulating NO-cGMP signalling pathway.

L-arginine and tetrahydrobiopterin, but not sodium nitrite partially restored erectile dysfunction in aged rats.

Aging is associated with erectile dysfunction (ED), in which nitric oxide synthase (NOS) activity and NO bioavailability are reduced due to deficiencies of NOS cofactor (tetrahydrobiopterin, BH(4)) and substrate (L-arginine). We determined whether the prolonged treatment with sodium nitrite (NaNO(2)) as a storage form of NO ameliorates ED in aged rats. Male Sprague-Dawley rats were divided: younger, aged and NaNO(2)-treated (20 mg/kg per day) aged groups. The erectile (intracavernosal pressure [ICP]/mean arterial pressure [MAP]) and corpus cavernous (CC) responses were evaluated after 12 weeks. The ICP/MAP in aged rats was lower than in young controls, which was not improved by the NaNO(2) treatment. Immunohistochemical (IHC) staining for endothelial NOS and collagen deposition was performed. We assayed NO indirectly by measuring the level of its stable end products, nitrite/nitrate, using the Griess reagent. The relaxations to ACh and EFS in the aged group were considerably less than in the younger group, which were normalized by acute incubations of l-arginine or BH(4) of aged CC. In conclusion, NaNO(2) treatment did not restore erectile response while nitrate levels were enhanced in aged penis. The cofactor or substrate administrations, but not chronic exogenous modulation of NO system may be beneficial in aged men with ED.