Contractile effect of substance P on the canine urinary bladder in vivo

Recent immunohistochemical studies have demonstrated a supply of polypeptides in neurons in many peripheral tissues including the lower urinary tract. The presence of substance P (SP) in the urinary bladder have been documented. In previous in vitro studies on isolated bladder muscle strips SP was found to have a contractory effect. In the present in vivo study intravesical pressure and arterial pressure were recorded following intraarterial administration of SP into six adult female dogs. Following administration of SP in doses of 0.1–0.75 μg/kg body weight (BW) no effect on intravesical pressure and a short-lasting decrease in arterial blood pressure were recorded. Following SP in doses of 1–10 μg/kg BW an immediate and moderate increase in intravesical pressure and marked and longlasting decrease in intraarterial blood pressure were recorded. On the basis of the previous in vitro and immunohistochemical studies and the present in vivo study, the role of SP as a modulator of tone and motility of the urinary bladder should be considered.     

Nerve growth factor and substance P: expression in a rat model of diabetic bladder

Objective  

To evaluate the gene and protein expression of nerve growth factor (NGF) and substance P (SP) in the bladder 8 weeks after diabetes induction and investigate the pathogenesis of diabetic cystopathy.     

P物质在异氟烷诱发脊髓损伤大鼠神经源性肺水肿中的作用

[目的]探讨吸入异氟烷的大鼠急性脊髓损伤后血清和肺泡灌洗液中P物质含量的改变与神经源性肺水肿的关系.[方法]成年雄性SD大鼠30只,体重300～330 g,随机分为1.5%异氟烷组、水合氯醛组和假手术组,每组10只.在T8水平球囊扩张造成脊髓压迫,压迫结束10 min后处死大鼠.检测各组大鼠血清和肺泡灌洗液中P物质含量和蛋白浓度,计算肺通透指数.[结果]1.5%异氟烷组大鼠血清和肺泡灌洗液中P物质高于水合氯醛组(P<0.05),明显高于假手术组(P<0.01);肺通透指数1.5%异氟烷组也高于水合氯醛组和假手术组(P<0.05).水合氯醛组和假手术组的P物质及肺通透指数均没有明显差异(P>0.05).[结论]1.5%异氟烷可能通过刺激P物质的大量释放参与急性脊髓损伤后肺水肿的形成过程.     

大鼠急性颈脊髓损伤后P物质与肺水肿的关系

目的 :探讨大鼠急性颈脊髓损伤后P物质与肺水肿的关系。方法 :成年Wistar大鼠40只,体重240~250g,雌雄不限,随机分为实验组和对照组,每组20只,每组又分为造模后24h、3d、1周、2周共4个时间点,每个时间点5只大鼠。实验组采用改良Allen′s打击法制作大鼠C7急性脊髓损伤(SCI)模型,打击力度为10×2.5g.cm;对照组只暴露C7段脊髓。在造模后相应时间点处死大鼠,通过光学显微镜观察肺组织的病理学变化,并检测各时间点两组大鼠血清和肺泡灌洗液中P物质含量和蛋白浓度,计算肺通透指数(肺泡灌洗液蛋白浓度/血清蛋白浓度)。结果:实验组大鼠急性SCI后24h肺组织可见肺毛细血管充血,肺泡内分泌物增多、红细胞增加;伤后3d达到高峰;伤后1周肺泡内水肿、出血较3d时减轻;伤后2周明显好转;对照组肺泡透亮,无水肿和出血。实验组伤后24h血清和肺泡灌洗液中P物质升高,伤后3d达高峰,伤后1周开始下降,伤后2周明显下降;实验组伤后24h、3d、1周血清及伤后24h、3d肺泡灌洗液中P物质含量与对照组比较有显著性差异(P<0.05),伤后2周两组比较无显著性差异(P>0.05)。肺通透指数的变化与P物质的变化趋势相同。结论:大鼠急性颈SCI后肺泡灌洗液及血清中P物质含量变化与肺水肿程度变化同步,P物质可能参与了急性颈SCI后肺水肿的形成过程。     

Chronic inflammation and bladder cancer

The relation between Schistosomiasis and bladder cancer is well-established and accounts for the high rates of bladder cancer in a number of developing countries, including Egypt. In developed countries, transitional cell carcinoma is the predominant type of bladder cancer, whereas in Schistosomiasis-endemic regions, squamous cell carcinoma is the most common type. In this review, experimental and observational data on infection, inflammation, and bladder cancer are summarized with special emphasis on transitional cell carcinoma. Findings from numerous studies suggest that inflammation is likely to have an important role in bladder carcinogenesis in developed countries. Future studies need to focus in greater detail on risk factors that increase inflammation of the bladder, examine genetic susceptibility to inflammatory pathways, and include markers of inflammation measured prior to cancer diagnosis. Understanding the role of inflammation on transitional cell carcinogenesis may provide important insights on how to prevent the sixth most common cancer in the United States.     

Intrathecal administration of substance P in the rat: the effect on bladder and urethral sphincteric activity.

At the lumbosacral spinal cord level in the rat, substance P-positive neurons are present in dense concentration in the dorsal horn and the sacral parasympathetic nucleus. We undertook the present study to investigate the effect of intrathecal substance P (10 micrograms at the L6-S1 level) on urinary bladder and urethral sphincteric activity and to compare these effects with those of intravenous and intra-arterial administration. Three different bladder pressure responses were triggered by intrathecal substance P: (A) an immediate, strong bladder contraction (n = 5); (B) augmentation of the micturition reflex, as indicated by strong detrusor contractions in response to intravesical saline perfusion (n = 4); and (C) a slow, gradual increase to a high, steady peak (n = 8). The sphincteric electromyographic (EMG) activity was consistently increased. When substance P was given intravenously (n = 10) and intra-arterially (n = 3), the form, duration, and maximal amplitude of bladder contractions (owing to a direct smooth-muscle action) were comparable with those of Group A. The effects in intrathecal Groups B and C suggest that substance P provides a tonic influence on motor horn cells and on the preganglionic neurons in the sacral parasympathetic nucleus at the lumbosacral spinal cord level, where neuronal circuits controlling bladder and sphincteric activity are located.     

Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation

OBJECTIVE

To determine the effect of botulinum toxin type A (BTX‐A) on the release of the neuropeptides substance P (SP) and calcitonin gene‐related peptide (CGRP) from isolated bladder preparations after acute injury with HCl and the induction of cyclophosphamide (CYP)‐induced cystitis, as neurogenic inflammation has been increasingly identified in urological disorders such as interstitial cystitis.

MATERIALS AND METHODS

Adult rats had either an intraperitoneal injection with CYP or saline over a 10‐day period to induce chronic bladder inflammation, after which the bladder was harvested, or normal bladder explants were injured acutely with incubation (20 s) in HCl (0.4 m ). To measure the effect of BTX‐A on the release of neurotransmitters, harvested bladders were incubated in an organ bath containing BTX‐A (10 U) or vehicle. Bladders were transferred to a subsequent bath (physiological saline) and incubated for 15 min, and the bathing medium analysed to measure neurotransmitter release, as determined by radioimmunoassay. Bladder specimens from sham treatment, controls and experimental rats were compared histologically.

RESULTS

Acute injury with HCl caused a significantly greater release of both CGRP and SP release (1235 and 1655 pg/g, respectively) than in controls (183 and 449 pg/g, respectively; P < 0.001). This increase in neurotransmitter release was partly inhibited by exposure to BTX‐A (870 and 1033 pg/g (P < 0.05 and <0.01). CYP‐induced chronic inflammation caused significantly greater release of SP than in the controls (1060 and 605 pg/g, respectively; P < 0.005). Exposure to BTX‐A partly inhibited the release of SP after CYP‐induced cystitis (709 pg/g, P < 0.05).

CONCLUSIONS

The application of BTX‐A inhibits the release of sensory neurotransmitters from isolated bladder preparations in rat bladder models of both acute injury and chronic inflammation, suggesting a potential clinical benefit of BTX‐A in the treatment of neurogenic inflammation.     

Animal models of bladder cancer

Treatment with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) or N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) in the drinking water induces bladder cancer of rats or mice with high incidence. Induced bladder cancers of rats are mostly papillary, non-invasive type, whereas those of mice are non-papillary, invasive type. Histologically, most of BBN-induced bladder cancers are transitional cell carcinoma in both rats and mice. On the other hand, the incidences of squamous cell carcinoma increased in cases of mice, especially in mice treated with EHBN. Metastases and invasions of bladder cancers are more common in mice than in rats. There are strain and species differences in the bladder response to BBN and EHBN. In addition, a putative preneoplastic lesion, papillary or nodular hyperplasia of the epithelium is a good marker for early detection of bladder cancer development.     

糖尿病大鼠膀胱中P物质、神经生长因子表达及氧化应激状态的研究

目的 研究糖尿病大鼠膀胱中P物质、神经生长因子(NGF)的表达及氧化应激状态的改变. 方法雄性Wistar大鼠分3组:对照组(n=10),糖尿病组(n=10),治疗组(n=10,糖尿病大鼠胃管注入太得恩(R),100 mg·kg-1·d-1).8周后取出膀胱,RT-PCR法检测膀胱组织中NGF表达,免疫组化方法检测P物质及一氧化氮合酶(iNOS)的表达,采用生化方法检测过氧化氢酶(CAT)、过氧化物酶(SOD)和丙二醛(MDA)水平.结果 糖尿病组膀胱组织中NGF mRNA表达水平中位值(0.35)显著低于对照组(2.77,P＜0.05),P物质表达水平(9.83)显著低于对照组(28.81,P＜0.05),CAT及SOD水平(11.46,7.16 U/mg蛋白)显著低于对照组(16.01,21.436 U/mg蛋白,P＜0.05),iNOS及MDA水平(67.50,15.97 nmol/mg蛋白)显著高于对照组(0,7.95 nmol/mg蛋白,P＜0.05).治疗组膀胱组织中NGF mRNA表达水平中位值(1.84)显著高于糖尿病组(P＜0.05),P物质表达水平(20.75)显著高于糖尿病组(P＜0.01),CAT及SOD水平(14.47,16.641 U/rag蛋白)显著高于糖尿病组(P＜0.05),iNOS及MDA水平(13.20,10.99 nmol/mg蛋白)显著低于糖尿病组(P＜0.05).结论 氧化应激存在于糖尿病大鼠膀胱.NGF、P物质在糖尿病膀胱中低表达.太得恩能增强糖尿病大鼠膀胱中NGF及P物质表达,改善氧化应激状态.     

Role for osteoprotegerin in rheumatoid inflammation

Osteoprotegerin (OPG), a member of the TNF-receptor family expressed by osteoblasts, has documented effects on the regulation of bone metabolism. OPG inhibits bone resorption and binds with strong affinity to its ligand RANKL, thereby preventing RANKL from binding to its receptor RANK. This system is regulated by calcium-modifying hormones. OPG may also be pivotal in modulating the immune system. RANKL-deficient mice exhibit both severe immunological abnormalities and osteopetrosis, and activated T cells express RANKL mRNA. RANKL secretion by activated T cells may induce osteoclastogenesis via a mechanism enhanced by several cytokines (TNF-alpha, IL-1, and IL-17) that promote both inflammation and bone resorption. Conversely, this mechanism is inhibited by OPG, IL-4, and IL-10, which have antiinflammatory effects and inhibit osteoclast formation. Activated T cells in the rheumatoid synovium express RANKL. Synoviocytes can differentiate to osteoclast-like cells under specific conditions, particularly when they are cultured with M-CSF and RANKL. Thus, the bony erosions seen in RA may result from RANKL/RANK system activation by activated T cells. This raises the possibility that OPG therapy to block this mechanism might prove beneficial in patients with RA.     

Role models in surgery

Our present training models date back almost 100 years. It is very apparent that trying to reshape an ageing system to meet the demands of today's patients and their physicians is just not going to be effective or efficient. In the past educators cared little about the working conditions for trainees such as the living and learning environment, social support and compensation models. You were just fortunate to be “chosen”. Surgical educators in the 21st Century must reexamine their roles and consider what message they are sending to future generations on these and other critical issues that impact on safe patient care.     

增生性瘢痕P物质含量的放射免疫测定

目的测定增生性瘢痕组织中P物质含量是否高于非增生性瘢痕及正常皮肤。方法用放射免疫法分别对增生性瘢痕、非增生性瘢痕及正常皮肤组织中P物质含量做定量分析研究。结果增生性瘢痕组织中P物质含量显著高于非增生性瘢痕及正常皮肤组织(P<0.01)。结论 P物质在增生性瘢痕的发病过程中可能起重要作用。     

增生性瘢痕P物质含量的放射免疫测定

目的测定增生性瘢痕组织中Ｐ物质含量是否高于非增生性瘢痕及正常皮肤。方法用放射免疫法分别对增生性瘢痕、非增生性瘢痕及正常皮肤组织中Ｐ物质含量做定量分析研究。结果增生性瘢痕组织中Ｐ物质含量显著高于非增生性瘢痕及正常皮肤组织（Ｐ＜０．０１）。结论Ｐ物质在增生性瘢痕的发病过程中可能起重要作用。