阴茎勃起神经再生模型和机制的研究

探明神经性勃起功能障碍(NED)的分子生物学机制以期对该类疾病进行神经调控干预,是男科学研究的当务之急。本文回顾了急性神经损伤、前列腺癌、糖尿病和帕金森病所致的NED的研究进展。通过利用大鼠阴茎勃起神经的盆腔大神经节(MPG),在体外构建一个三维培养体系来研究各种生长因子和细胞信号通路对神经再生的影响。体外结果表明脑源性神经生长因子(BDNF)通过JAK/STAT信号通路可显著促进NED的恢复,并在体内证实了该效应。因此,通过调控JAK/STAT信号通路来达到神经调控干预措施预防治疗神经性勃起功能障碍成为可能。     

Fibroblast growth factor 23 regulates renal 1,25‐dihydroxyvitamin D and phosphate metabolism via the MAP kinase signaling pathway in Hyp mice

In X‐linked hypophosphatemia (XLH) and in its murine homologue, the Hyp mouse, increased circulating concentrations of fibroblast growth factor 23 (FGF‐23) are critical to the pathogenesis of disordered metabolism of phosphate (P_i) and 1,25‐dihydroxyvitamin D [1,25(OH)₂D]. In this study, we hypothesized that in Hyp mice, FGF‐23‐mediated suppression of renal 1,25(OH)₂D production and P_i reabsorption depends on activation of mitogen‐activated protein kinase (MAPK) signaling. Wild‐type and Hyp mice were administered either vehicle or the MEK inhibitor PD0325901 (12.5 mg/kg) orally daily for 4 days. At baseline, the renal abundance of early growth response 1 (egr1) mRNA was approximately 2‐fold greater in Hyp mice than in wild‐type mice. Treatment with PD0325901 greatly suppressed egr1 mRNA abundance in both wild‐type and Hyp mice. In Hyp mice, PD0325901 induced an 8‐fold increase in renal 1α‐hydroxylase mRNA expression and a 4‐fold increase in serum 1,25(OH)₂D concentrations compared with vehicle‐treated Hyp mice. Serum P_i levels in Hyp mice increased significantly after treatment with PD0325901, and the increase was associated with increased renal Npt2a mRNA abundance and brush‐border membrane Npt2a protein expression. These findings provide evidence that in Hyp mice, MAPK signaling is constitutively activated in the kidney and support the hypothesis that the FGF‐23‐mediated suppression of renal 1,25(OH)₂D production and P_i reabsorption depends on activation of MAPK signaling via MEK/ERK1/2. These findings demonstrate the physiologic importance of MAPK signaling in the actions of FGF‐23 in regulating renal 1,25(OH)₂D and P_i metabolism. © 2011 American Society for Bone and Mineral Research     

Effect of extended-term estrogen on voiding in a postpartum ovariectomized rat model

Introduction

We tested the hypothesis that extended-term (5-week) estrogen therapy would negatively impact voiding function in a postpartum, ovariectomized rat model.

Methods

Immediately after delivery, 30 primiparous Sprague–Dawley rats underwent intravaginal balloon dilation, followed by ovariectomy 1 week later. Cystometry at postpartum week 2 determined normal or abnormal voiding patterns. After randomization, one-half the normal and abnormal voiding rats received 5 weeks of estrogen therapy, while the remainder received placebo. Estrogen effect was determined by repeat cystometry and immunohistochemical analysis of the urethra and vagina.

Results

Abnormal voiding increased from 60.0% to 73.3% in the estrogen- treated group and declined from 60% to 33% for the placebo group. Rats were then divided into 4 groups for comparison: normal voiding versus placebo (group 1), abnormal voiding versus placebo (group 2), normal voiding versus estrogen (group 3) and abnormal voiding versus estrogen (group 4). Bladder capacity, leak point pressure and maximum voiding pressure were most depressed in group 4. Estrogen treatment was associated with a significant downregulation of α_1A and α_1D-adrenoceptors in the urethral submucosa but an upregulation of nNOS in the urethral smooth muscle.

Conclusion

Extended-term estrogen therapy in a rat model of simulated birth trauma and ovariectomy resulted in a higher rate of incontinence. Immunohistochemical examination demonstrated significant downregulation of urethral α_1A- and α_1D-adrenoceptors and upregulation of neuronal nitric oxide synthase (nNOS) in the urethra of estrogen-treated groups. These studies question the use of hormone replacement therapy in the treatment of postmenopausal incontinence.     

侧脑室计算机三维重建及理论分析

目的 :建立便于推广、功能齐全、价廉的三维医学图像重建系统及进行三维重建。方法 :利用目前较先进的数码摄片技术和自行编制的软件系统 ,对层距 1.0 mm的人体头部断面共 2 4 0层进行侧脑室的三维重建 ,同时对头部整体行三维重建以其进行相对定位和比较。结果 :重建后的侧脑室可和头部进行参照显示 ,行旋转、透明处理和不同方向的任意剖割。结论 :较以 CT、MRI断面图像重建的模型增加了轮廓的准确性和器官内组织的鲜明色彩     

假细锥香茶菜新二萜成分——假细锥甲素的结构

从假细锥香茶菜(Rabdosia coetsoides C.Y.Wu)叶分离得到新二萜成分,根据紫外光谱、红外光谱、质谱、核磁共振氢谱及碳谱等分析,推定了化学结构,并经X-射线衍射确证,命名为假细锥甲素。     

Detailed anatomy of penile neurovascular structures: surgical significance

In 10 formalin-preserved adult male cadavers, dissection of the penile veins, arteries and nerves revealed information of clinical importance. The main venous drainage of the corpora cavernosa is via the cavernous veins, with additional drainage through the circumflex, deep dorsal, and crural veins. The arterial supply of the cavernous bodies varied remarkably, and the incidence of an accessory internal pudendal artery was high. The cavernous nerves, previously believed to be microscopic structures, were in fact identifiable grossly, and we were able to follow them from the region of the hilum of the penis to the prostate. The nature of these nerves was then confirmed by serial histologic sectioning. This detailed knowledge of the venous drainage and arterial and nervous supply of the penis, as well as of the relationships among the cavernous structures in the hilum of the penis, can elucidate the cause of erectile dysfunction and provide a valuable guide for surgical correction of vasculogenic and neurogenic impotence.     

Spinal anesthesia and electroerection in dogs and monkeys

We studied the penile erectile response to cavernous nerve electrostimulation in five monkeys and eight dogs before and during spinal anesthesia. Anesthesia was obtained by intradural injection (at L4-L5 level) of either xylocaine (two mg./kg. body weight) or tetracaine (0.2 mg./kg.). In monkeys, systolic blood pressure reduction (average 17.2%), slight elongation and tumescence of the penis, and increase of intracavernous pressure were noted after spinal anesthesia. Electrostimulation of the cavernous nerves resulted in longer erection and detumescence phases than obtained before anesthesia. In dogs, a similar blood pressure decrease (16.6% average) was noted after anesthesia. The response during anesthesia to electrostimulation of the erectile nerves was, however, variable. Changing the animal's position abolished the erectile response in three of four dogs while no change of erectile response due to anesthesia could be demonstrated in the remaining four dogs. We conclude that spinal anesthesia seems to enhance simian, but not canine, erectile response to electrostimulation of the erectile nerves, possibly via interference of the autonomic regulatory mechanism.     

Vestibular evoked myogenic potentials are heavily dependent on type I hair cell activity of the saccular macula in guinea pigs

This study applied the vestibular evoked myogenic potential (VEMP) test to guinea pigs coupled with electronic microscopic examination to determine whether VEMPs are dependent on type I or II hair cell activity of the saccular macula. An amount of 0.05 ml of gentamicin (40 mg/ml) was injected directly overlaying, but not through, the round window membrane of the left ear in guinea pigs.One week after surgery, auditory brainstem response test revealed normal responses in 12 animals (80%), and elevated thresholds in 3 animals (20%). The VEMP test using click stimulation showed absent responses in all 15 animals (100%). Another 6 gentamicin-treated animals underwent the VEMP test using galvanic stimulation and all 6 also displayed absent responses. Ultrathin sections of the saccular macula in the gentamicin-treated ears displayed morphologic alterations in type I or II hair cells, including shrinkage and/or vacuolization in the cytoplasm, increased electron density of the cytoplasm and nuclear chromatin, and cellular lucency. However, extrusion degeneration was rare and only present in type II hair cells. Quantitative analysis demonstrated that the histological density of intact type I hair cells was 1.1 +/- 1.2/4000 microm(2) in the gentamicin-treated ears, showing significantly less than that in control ears (4.5 +/- 1.8/4000 microm(2)). However, no significant difference was observed in the densities of intact type II hair cells and supporting cells between treated and control ears. Furthermore, the calyx terminals surrounding the damaged type I hair cells were swollen and disrupted, while the button afferents contacting the damaged type II hair cells were not obviously deformed. Based on the above results, we therefore conclude that VEMPs are heavily dependent on type I hair cell activity of the saccular macula in guinea pigs.     

The diagnosis of venogenic impotence: dynamic or pharmacologic cavernosometry?

In an attempt to refine the diagnosis of venogenic impotence, we evaluated different techniques of cavernosometry in 10 dogs. Saline was perfused intracavernously in five dogs to induce erection. Regardless of the amount required for induction, a mean flow rate of 23.4 ml./min. was necessary to maintain an intracavernous pressure level of 110 cm. H2O. In seven dogs, a leak was created by intracavernous insertion of a 19-gauge needle. When erection was induced by either cavernous nerve stimulation or a combination of papaverine injection and saline perfusion, the mean flow through the needle was significantly less than when erection was induced by saline perfusion alone (1.73, 1.78, and 8.77 ml./min., respectively). Sympathetic trunk stimulation at the level of L5 could reduce the intracavernous pressure by 90% in erections induced by neural stimulation or papaverine plus perfusion but had no effect on erection induced by saline perfusion alone. Our findings show that cavernosometry after intracavernous injection of papaverine will provide more valuable information in patients in whom venogenic impotence is suspected.