Maintenance of the contractile phenotype in corpus cavernosum smooth muscle cells by Myocardin gene therapy ameliorates erectile dysfunction in bilateral cavernous nerve injury rats.

The pathophysiology of erectile dysfunction post radical prostatectomy is not clearly clarified, and the low efficacy of traditional PDE5i treatment remains a major complaint in contemporary practice. This study aimed to demonstrate phenotypic modulation in bilateral cavernous nerve injury (BCNI) rats within 7 days, and subsequently validate gene therapy with Myocardin (Mycod) by maintaining a contractile phenotype in corpus cavernosum smooth muscle cells. Initially, 36 male rats were randomly divided into BCNI and negative control (NC) groups for histological and phenotypic molecular measurements at 3, 5, and 7 days. Afterwards, an additional 30 rats received a single intra-cavernous injection of 50 µL PBS, Ad-Myocd (1 × 1011  pfu/ml) or Ad-vector for 10 animals each, namely the NC+PBS, BCNI+Ad-Myocd, and BCNI+Ad-vector groups. Finally, the validity and mechanism of Myocd transfection was explored at 21 days in vivo and 48 h in vitro. Western blotting showed canonical declines in Myocd, α-SMA, and Calponin expression, as well as elevated Osteopontin (OPN) expression, before corporeal morphological and SM-to-collagen ratio changes at day 5 after injury. Overexpression of Myocd maintained the contractile phenotype of corpus cavernosum smooth muscle cells, ameliorated bilateral cavernous nerve injury rat erectile dysfunction, as well as promoted cell contractility and suppressed proliferative capacity. Simultaneously, confocal imaging revealed up-regulation and co-localization of serum response factor in gene-transferred cells. In conclusion, our study is the first to investigate corpus cavernosum smooth muscle cells phenotypes in the early stages of cavernous injury model rats, and Myocd reversed phenotypic modulation by activating serum response factor. The experimental results demonstrated the validity of gene therapy for erectile dysfunction.

Effect of chronic hypoxia on penile erectile function in rats.

We examined the relationship between chronic hypoxia and erectile dysfunction in rat and its possible pathogenic mechanism. Forty-eight white male adult Sprague-Dawley rats were randomly divided into a test group and a control group. In accordance with the experimental time (2, 6, and 10 weeks), each group was divided into 3 subgroups, with 8 rats in each subgroup. Rats in the test group were fed in an airtight hypoxia cabin, while rats in the control group were maintained in a normal environment, with other conditions kept the same. At 2, 6, and 10 weeks, the rats in each group were observed for erectile function. Affinity purification was used to detect neural nitric oxide synthase (nNOS)-positive nerve fibers and endothelial nitric oxide synthase (eNOS) expression. After hypoxia, erectile frequency decreased significantly compared to before hypoxia (P < 0.001). Comparison of the test group and control group revealed a significant difference in the quantity of nNOS-positive nerve fiber and eNOS protein expression (P < 0.01). Hypoxia may influence erectile function and nNOS and eNOS expression in rats. The decrease in the quantity of nNOS nerve fibers and expression of eNOS may contribute to erectile dysfunction under hypoxic conditions in rats.

Metabolic syndrome and risk for ED: a meta-analysis.

There are many recent observational studies on metabolic syndrome (MS) and the risk for ED, and it is still inconclusive whether MS increases the risk for ED. This meta-analysis aims to detect a relationship between MS and ED. We identified eligible studies by searching PubMed, Embase and the Cochrane Library for articles published before August 2013. Adjusted relative risks (RR) with 95% confidence interval (CI) were calculated using random-effects or fixed-effects models. A total of 10 studies involving 4092 participants were included in the meta-analysis. MS was associated with an increased incidence of ED (RR=1.60, 95% CI=1.27-2.02, P<0.001), with significant evidence of heterogeneity among these studies (P for heterogeneity <0.001, I(2)=92.9%). The subgroup and sensitivity analyses confirmed the stability of the results and no publication bias was detected. The present meta-analysis suggests that MS is significantly associated with the risk for ED. Large-scale and well-designed prospective studies are required to further investigate the association between MS and risk for ED.

The insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene and erectile dysfunction risk: a meta-analysis.

Erectile dysfunction (ED) is increasingly recognized as a public health problem. Several studies have reported the influence of the insertion/deletion (I/D) polymorphism in the Angiotensin-converting enzyme (ACE) gene on ED susceptibility, but the results remain controversial. To derive a more precise estimation of the relationship, a meta-analysis was conducted using data published previously by other groups. A total of six case-control studies, including 1039 cases and 927 controls, were selected. The pooled odds ratios (ORs) and respective 95% confidence intervals (CIs) were calculated by comparing the carriers of D-allele with the wild homozygotes (ID + DD vs. II). Comparisons of other genetic models were also performed (ID + II vs. DD, DD vs. II, DI vs. II and D vs. I). In the overall analysis, no significant association between the polymorphism and ED risk was observed (OR=1.07, 95% CI = 0.84 - 1.37, p = 0.575 for ID + DD vs. II). In the subgroup analysis by ethnic, no significant association was detected among Asian, Latino and European for the comparison of ID + DD vs. II (Asian: OR=1.27, 95% CI = 0.89 - 1.81; Latino: OR=0.76, 95% CI = 0.46 - 1.27; European: OR=1.06, 95% CI = 0.67 - 1.66). Results from other comparative genetic models also indicated the lack of associations between this polymorphism and ED risk. In conclusion, this meta-analysis indicates that the ACE I/D polymorphism might not contribute to the risk of ED.

Characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction.

Phenotypic modulation from a contractile to a proliferative state within vascular smooth muscle cells has a critical role in the pathogenesis of a variety of cardiovascular diseases. To investigate the characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction, a group of Sprague-Dawley rats (n=30) were induced by intraperitoneal injection of streptozotocin (60 mg kg(-1)) and screened by subcutaneous injection of apomorphine (100 µg kg(-1)) for the measurement and comparison of the penile erections, and then three different groups were defined. Primary corpus cavernosum smooth muscle cells were cultured and passaged. The cavernous tissue segments were subjected to quantitative real-time polymerase chain reaction to determine the expressions of smooth muscle α-actin (SMA), SM myosin heavy chain (SMMHC), smoothelin, calponin and myocardin. Cell contractility in vitro and western blot analysis of SMA and SMMHC in the cavernous tissues and cells were determined. Compared with the control group (n=8) and the diabetes mellitus group (n=5), the expressions of SMA, calponin, SMMHC, smoothelin and myocardin mRNA were decreased in the cavernous tissues in rats of the diabetic erectile dysfunction group (n=15; P=0.001 and 0.02, P=0.014 and 0.012, both P<0.001, P=0.005 and <0.001, P=0.003 and 0.035, respectively). The levels of SMA and SMMHC proteins showed a significant decrease in cavernous tissues and cultured cells in rats of the diabetic erectile dysfunction group. Cells of the diabetic erectile dysfunction group exhibited significantly less contractility compared with those of other groups (P<0.001). Corpus cavernosum SM cell possesses the ability to modulate the phenotype under hyperglycemic conditions, which could have a key role in the pathogenesis of diabetic erectile dysfunction.

Reduced expression of myocardin and serum response factor in the cavernous tissue of diabetic rats.

This study aimed to investigate the expression of myocardin and serum response factor (SRF) in the cavernous tissue of diabetic rats. The experimental diabetes model was induced in 8-week-old male Sprague-Dawley rats (200-220 g) by a single administration of streptozotocin. Both the diabetes mellitus group (DM group, n = 20) and the control group (NDM group, n = 10) were injected with a low dose of apomorphine to allow for the measurement and comparison of the corresponding penile erections. Western blot and qRT-PCR were used to determine the protein and mRNA expression levels of myocardin and SRF. Erectile function was significantly decreased in the DM group compared with the control group (P < 0.001). The mRNA and protein expression levels of myocardin and SRF were reduced in the cavernous tissue of diabetic rats compared with the control group (P < 0.001). It is concluded that diabetes inhibits the mRNA and protein expression of both myocardin and SRF in the cavernous tissue. This could play a key role in the development of erectile dysfunction in diabetic rats.

Saline contrast sonohysterography and directed extraction, resection and biopsy of intrauterine pathology using a Uterine Explora Curette.

OBJECTIVE: To assess the utility of an endometrial sampling device, the Uterine Explora Curette, with concomitant saline contrast sonohysterography (SCSH) for ultrasound-directed extraction, resection and biopsy of endometrial pathology. METHODS: Use of the Uterine Explora Curette was prospectively evaluated in 20 women with either infertility (n = 14), recurrent miscarriage (n = 2) or peri-/postmenopausal bleeding (n = 4). Findings on SCSH were compared with those on pathological analysis. RESULTS: In all 20 cases the Uterine Explora Curette was used successfully during SCSH to treat endometrial filling defects. The procedure was well tolerated, with an average time from start to finish of 10 (range, 2-23) min. It was without complications, and appeared to remove or biopsy adequately endometrial filling defects in most patients, obviating the need for hysteroscopy. CONCLUSIONS: In properly selected patients, directed extraction, resection and biopsy using the Uterine Explora Curette during SCSH appears to be an effective and easy method for treating intrauterine pathology and provides a cost-effective alternative to operative hysteroscopy.

[Clinical study on combined treatment of shuizhi tuyuan powder and nifedipine in treating hypertension patients complicated with left ventricular hypertrophy].

Patients with essential hypertension complicated with left ventricular hypertrophy (LVH) confirmed by ultrasonic cardiography were divided randomly into observation group and control group. Both groups were treated with nifedipine. Shuizhi Tuyuan Powder (SZTYP, consisted of Hirudo nipponia and Eupolyphaga sinensis) was given in addition to the observation group. The therapeutic course for the two groups were 6 months. Results showed that after one course of treatment, the myocardial weight index lowered from 136.8 +/- 7.5 g/m2 to 130.5 +/- 6.4 g/m2 in observation group, while in control group, it lowered from 136.7 +/- 7.4 g/m2 to 134.3 +/- 6.2 g/m2, the difference between the two groups was significant (P < 0.01). The symptoms were relieved in part of the patients with early stage of cerebrovascular disease treated with SZTYP. The results suggested that SZTYP combined with nifedipine has active curative effect on essential hypertension patients complicated by LVH and part patients in early stage of cerebrovascular disease.

Increased expression of a 68-kDa protein in the corpus cavernosum of some men with erectile dysfunction.

Erectile dysfunction (ED) may be caused by abnormalities of intracavernous penile structures. In order to investigate whether specific proteins could be identified that might be related to ED, the composition of structural proteins in cavernous tissues of patients with ED was compared to that of normal cavernous tissues by gel electrophoresis. Increased expression of a 68-kDa nonionic detergent extraction-resistant protein was demonstrated in tissues of more than half of the patients with vasculogenic ED, whereas only one out of nine normal cavernous tissues showed the same phenomenon. Increased expression was not related to a specific type of vascular insufficiency, aging, or diabetic constituency. Histochemical and immunochemical studies revealed that the increased amount of the 68-kDa protein is not merely the result of a surplus of nervous, smooth muscle, or elastic tissues. Furthermore, antibodies specific for 68-kDa neurofilament and 62- to 67.5-kDa tropoelastin did not recognize the 68-kDa protein on Western blots. The possibility that the 68-kDa protein may help us understand the etiology of certain cases of erectile dysfunction is discussed.

[Effects of leech and ground beetle powder on hemorheology and blood lipid of ischemic stroke].

In order to improve blood supply for the brain, restore the functions of the cerebral cells and the limbs, and increas the curative rate, the leech (Hirudo nipponica and ground beetle Eupolyphage sinensis), powder (LGBP) to the patients according to the principle of promoting the blood circulation to remove the stasis was administered, and the clinical observation and experimental study was conducted. Its effects were compared with those of Western medicines. The results showed that after medication of LGBP, the blood flow of brain significantly increased, the hypoxia was improved, blood viscosity and blood lipid were lowered and thrombosis was inhibited in vitro or in vivo. No toxic side-effects caused by LGBP was found.