Muscle Shortening Along the Normal Esophagus During Swallowing

Longitudinal shortening of the esophagus during peristaltic contraction has been previously analyzed globally using spaced mucosal clips. This method gives a relatively crude measurement. In this study, local longitudinal shortening (LLS) was evaluated using simultaneous high-resolution endoluminal ultrasound (HREUS) and manometry based on basic principles of muscle mechanics. We sought to determine if there are regional differences in LLS of the esophageal muscle during swallow-induced peristaltic contraction and evaluate shortening of the circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the esophagus. Twenty normal subjects underwent simultaneous HREUS/manometry at 4 levels (5, 10, 15, and 20 cm above the upper border of the lower esophageal sphincter [LES] high-pressure zone) in the esophagus with 5-mL swallows of water. Ultrasound images were recorded with synchronized manometric pressure data. The images were digitized and the cross-sectional surface area (CSA) of the LSM, CSM, and total muscle (TM) were measured at baseline (at rest) and at peak intraluminal pressure (implying peak CSM contraction) during swallowing. LLS was calculated for the CSM and LSM using the principle of mass conservation, whereby the change in CSA relative to the resting CSA is quantitatively equal to the relative change in length of a local longitudinal muscle segment. CSM, LSM, and TM all shortened longitudinally, with the circular muscle shortening more than the longitudinal muscle, LLS of the CSM and TM layers at 5 cm above the LES was significantly greater than at 20 cm (CSM: 30% difference, P < .001; TM: 18% difference, P < .05). The greater shortening of LSM at 5 versus 20 cm was found not to be statistically significant (11% difference, P > .05). Peak intraluminal pressure strongly correlated with peak muscle thickness of all layers at all levels (r = 0.96–0.98). LLS increases from the proximal to the distal esophagus during bolus transport. CSM and LSM both shorten longitudinally, with CSM shortening more than LSM. The increase in LLS increases the efficiency of peristaltic contraction and likely contributes to the axial displacement of the LES preceding hiatal opening and esophageal emptying.     

Effect of Peroxynitrite on Motor Function of the Opossum Esophagus

Nitric oxide (NO·) is a mediator of esophageal motility. Esophageal dysmotility accompanies esophagitis. During inflammation, superoxide and NO· form peroxynitrite (ONOO^-), a reactive molecule that alters cellular function. We tested the hypotheses that ONOO^- affects esophageal motility and is produced in association with esophagitis. Transverse muscle strips from the opossum esophagus were stimulated by an electrical field, and nitrotyrosine immunoblots were performed. Peroxynitrite, its decomposed form, or NaNO₂ relaxed the lower esophageal sphincter (LES) and attenuated the off response. These effects were inhibited by oxyhemoglobin (Hgb). An antagonist of guanylate cyclase, 1H-[1,2,4]oxadiazole[4,3]quinoxalin-1-one (ODQ), inhibited the LES relaxation produced by ONOO^-. Nitrotyrosine, a footprint for ONOO^- production, was detected in inflamed esophagus. These studies support the hypotheses that ONOO^- alters esophageal motor function and is formed in association with esophagitis. It is possible that some of the esophageal motor dysfunction seen with esophagitis may be related to the formation of ONOO_-.     

细胞的相互作用对基质金属蛋白酶-1的影响

目的 :研究单核细胞与血管平滑肌细胞 (VSMCs)之间的相互作用对基质金属蛋白酶 - 1(MMP- 1)分泌的影响。　　方法 :将人类单核细胞与 VSMCs联合及隔离培养 ,用酶联免疫荧光法测定 MMP- 1水平 ,并用荧光标记胶原蛋白消化法测定 MMP- 1的活性。　　结果 :单核细胞与 VSMCs联合培养可明显增加 MMP- 1的水平和活性 ,当两种细胞之比为 1.0时达高峰 ;细胞间的直接接触及细胞因子可介导 MMP- 1的产生。　　结论 :单核细胞与 VSMCs之间的相互作用可促使 MMP- 1的产生及活性增加 ,可能在动脉粥样硬化斑块的破裂中起重要作用。     

基质金属蛋白酶与动脉损伤后再狭窄

心血管动脉系统在损伤后,包括经皮腔内血管成形术后血管再狭窄率较高,严重影响了手术的治疗效果。基质金属蛋白酶(MMPs)是一组能特异地降解细胞外基质成分的依赖锌的酶家族,在组织重构中起重要作用。了解MMPs表达和动脉损伤后再狭窄的关系有助于在机制上认识狭窄的动脉再成形术的再狭窄问题,从而为临床上治疗冠状动脉粥样硬化性心脏病提供新的途径。     

Dilation of Benign Strictures in the Esophagus and Colon with the Polyflex Stent: A Case Series Study

Polyflex, a new self-expanding plastic stent (SEPS), is increasingly used to treat obstructions in the gastrointestinal tract. The majority of reports on Polyflex come from tertiary referral centers. This retrospective study describes the efficacy and safety of this new SEPS for the treatment of benign strictures in esophagus and colon and its use in a community hospital. Seven patients were treated from August 2003 through December 2006. All of them presented with severe strictures, and were treated with Polyflex insertion. Four patients had esophageal obstructions (three peptic, one postoperative) and the remaining three patients had postoperative strictures in the rectosigmoid. One patient had a coexisting fistula. Two strictures (one esophageal and another colonic, both postoperative) received the Polyflex as the first line of treatment, without previous sessions of dilation. Esophageal strictures were solved after several consecutive SEPS insertions. Migrated stents were easily extracted from the stomach. On the other hand, colonic strictures achieved permanent dilation with a single stent. The patient with coexisting stricture and fistula became asymptomatic and still had the SEPS in place after four months. The one complication was mild pain after insertion. Polyflex seems to be a useful tool in the dilation of severe benign strictures in esophagus and rectosigmoid and, as in large centers, good results are achieved in a community hospital.     

Conditional and targeted overexpression of vascular chymase causes hypertension in transgenic mice

We cloned a rat vascular chymase (RVCH) from smooth muscle cells (SMCs) that converts angiotensin I to II and is up-regulated in SMC from spontaneously hypertensive vs. normotensive rats. To determine whether increased activity of RVCH is sufficient to cause hypertension, transgenic mice were generated with targeted conditional expression of RVCH to SMC, with the use of the tetracycline-controlled transactivator (tTA). We confirmed conditional expression of RVCH by mRNA, protein, and chymase activity in the absence, but not in the presence, of dietary doxycycline. The systolic blood pressure (mmHg), measured by carotid artery cannulation at 10-12 weeks of age, was higher in tTA+/RVCH+ mice than in nonbinary transgenic littermates (136 +/- 4 vs. 109 +/- 3) (P < 0.05), as were the diastolic and mean pressures. Hypertension was completely reversed by doxycycline, suggesting a causal link with chymase expression. Medial thickening of mesenteric arteries from tTA+/RVCH+ mice vs. littermates (0.82 +/- 0.1 vs. 0.42 +/- 0.02) (P < 0.05) was associated with increased SMC proliferation, as judged by positive immunoreactivity, with the use of an antibody to the proliferating cell nuclear antigen. These structural changes were prevented by doxycycline. Perfusion myography of mesenteric arteries from tTA+/RVCH+ mice also revealed increased vasoconstriction in response to phenylephrine and impaired metacholine-induced vasodilatation when compared with littermate controls or with the doxycyline-treated group. Our studies suggest that up-regulation of this vascular chymase is sufficient to cause a hypertensive arteriopathy, and that RVCH may be a candidate gene and a therapeutic target in patients with high blood pressure.     

N受体对四磨汤诱发的胃窦平滑肌收缩的影响

目的研究烟碱（N）受体对四磨汤诱发的sD大鼠离体胃窦平滑肌条收缩活动的影响。方法离体胃窦平滑肌条置于盛有Krebs液的组织浴槽中以记录其等长收缩活动,观察不同剂量四磨汤（1μL、5μL、25μL、50μL、100μL、150μL、200μL）对大鼠胃窦平滑肌条收缩活动的影响,并观察N受体阻断剂六烃季胺（10^-4mol／L）对四磨汤引起的胃窦平滑肌收缩活动的影响。结果四磨汤引起大鼠胃窦纵行和环行平滑肌条收缩活动增加呈剂量依赖性。六烃季胺对于四磨汤引起的胃窦纵、环形平滑肌条兴奋作用均具有部分抑制效应,对环行肌条的作用明显高于对纵行肌的影响。结论四磨汤对大鼠胃窦平滑肌的收缩活动具有明显的兴奋作用,但部分作用与N受体有关,胃窦环行肌更为依赖N受体的作用。     

Vasodilation and vascular control in contracting muscle of the aging human

There is accumulating evidence in humans that the control of blood flow to dynamically contracting skeletal muscle is altered with normal aging. Despite some inconsistencies in the literature, most healthy older subject groups studied to date (approximately 55-75 years) exhibited attenuated leg blood flow responses to moderate intensity leg exercise in comparison to younger (approximately 20-30 years) controls. In most cases, older subjects also have higher arterial perfusion pressures at rest and at any submaximal workload than their younger counterparts, suggesting a heightened level of vasoconstriction in the legs that could result from structural and/or functional alterations within the arterial vasculature. The influence of age on vasodilator responsiveness in the contracting limbs of humans remains an open question, with reports of blunted, similar, and augmented increases in local vascular conductance during graded exercise in older vs. younger adults. Recent results from the authors' laboratory suggest that the ability of vascular smooth muscle in the legs to dilate in response to physiological and pharmacological stimuli is relatively well preserved with advancing age in men; however, a sex difference may exist in that older estrogen-deficient women exhibit blunted leg vasodilator responses compared to younger women. Potential mechanisms underlying altered vascular control within the resistance vasculature of contracting muscles of older men and women remain to be determined, but could include (1) fewer, smaller, and/or stiffer vessels, (2) impaired endothelium-dependent vasodilation, (3) augmented sympathetic vasoconstriction, (4) alterations in metabolic or myogenic control, and (5) reduced effectiveness of the skeletal muscle pump. Systematic research involving both humans and animal models will be necessary to fully elucidate the mechanisms underlying compromised muscle blood flow in old age.     

胰岛素对糖尿病小鼠小肠功能的影响

Objective To investigate the effects of regular insulin (RI)on duodenal smooth muscle in diabetic mice. Methods Diabetes mellitus (DM) model was established by intraperitoneal injection of 150 mg/kg streptozotocin (STZ) in male BALB/c mice. The model mice were divided into DM group and DM treated with RI group with 6 each. Meanwhile, 6 normal mice were served as controls. The mice in treatment group were intraperitoneally injected with 40 U/kg of RI daily.Whereas the mice in DM and control groups were intraperitoneally injected with phosphate buffer solution (pH = 7. 40). After 6 weeks, the small intestinal transit rate of mice was determined by lavage of Indian ink. Interstitial cells of cajal (ICC) in duodenal myenteric plexus were counted using immunohistochemical staining. Slow waves of duodenal smooth muscle cells were recorded with intracellular recordings. Data were analysed by SPSS 17.0 software, and comparisons among three groups were done using LSD test. Results After intervention for 6 months, the clinical presentations,such as more water and food intake and polyuria, were improved in treatment group. The body weight was increased in treatment group [(23.33±3.13) g] compared with DM group [(15.42±1.40) g,P＜0.01] ,but dereased compared with control group [(26.78 ± 2.09) g, P＜0.05]. The level of blood glucose in DM group was significantly higher than that in control and treatment groups(P＜0.01). Small intestine transmission rate was significantly reduced in DM group than that in control and treatment groups (P＜0.01), but it was slower in treatment group than that in control group (P＜ 0. 01 ). Immunohistochemical study showed that the number of c-kit positive cells reduced obviously in DM group than that in control group and treatment group (P＜0.05), whereas it was lower in treatment group than that in control group (P ＜ 0.05). The slow wave frequency and amplitude of duodenal smooth muscle cells in DM group were reduced when compared with control and treatment groups (P＜0.01) and both were lower in treatment group than that in control group (P＜0. 01 ). Conclusion The findings indicate that DM mice have gastrointestinal dysmotility and exogenous insulin may improve small intestinal dysmotility in DM mice.     

四磨汤对胃窦平滑肌的影响及钙通道在其中的作用

目的研究四磨汤对SD大鼠离体胃窦纵、环行平滑肌条收缩活动的影响及钙通道在其中的作用。方法正常SD大鼠离体胃窦纵、环行平滑肌条置于盛有Krebs液的组织浴槽中,记录其等长收缩活动,观察四磨汤累积量加入(1μL、5μL、25μL、50μL、100μL、150μL、200μL)对大鼠胃窦纵、环行平滑肌条收缩活动的影响,以及钙通道阻断剂硝苯地平(30 nmol/L)对四磨汤引起的胃窦平滑肌条收缩活动的影响。结果四磨汤剂量依赖性引起大鼠胃窦纵、环行平滑肌条收缩活动增加,硝苯地平可部分阻断四磨汤对胃窦纵、环行平滑肌条的兴奋作用;硝苯地平对于四磨汤诱导的纵行肌兴奋的抑制效应明显强于环行肌。结论四磨汤对大鼠胃窦平滑肌的收缩活动具有明显的兴奋作用,这一兴奋作用部分通过钙通道介导,纵行肌较环行肌更多的依赖于外钙内流。     

胰岛素对糖尿病小鼠小肠功能的影响

Objective To investigate the effects of regular insulin (RI)on duodenal smooth muscle in diabetic mice. Methods Diabetes mellitus (DM) model was established by intraperitoneal injection of 150 mg/kg streptozotocin (STZ) in male BALB/c mice. The model mice were divided into DM group and DM treated with RI group with 6 each. Meanwhile, 6 normal mice were served as controls. The mice in treatment group were intraperitoneally injected with 40 U/kg of RI daily.Whereas the mice in DM and control groups were intraperitoneally injected with phosphate buffer solution (pH = 7. 40). After 6 weeks, the small intestinal transit rate of mice was determined by lavage of Indian ink. Interstitial cells of cajal (ICC) in duodenal myenteric plexus were counted using immunohistochemical staining. Slow waves of duodenal smooth muscle cells were recorded with intracellular recordings. Data were analysed by SPSS 17.0 software, and comparisons among three groups were done using LSD test. Results After intervention for 6 months, the clinical presentations,such as more water and food intake and polyuria, were improved in treatment group. The body weight was increased in treatment group [(23.33±3.13) g] compared with DM group [(15.42±1.40) g,P＜0.01] ,but dereased compared with control group [(26.78 ± 2.09) g, P＜0.05]. The level of blood glucose in DM group was significantly higher than that in control and treatment groups(P＜0.01). Small intestine transmission rate was significantly reduced in DM group than that in control and treatment groups (P＜0.01), but it was slower in treatment group than that in control group (P＜ 0. 01 ). Immunohistochemical study showed that the number of c-kit positive cells reduced obviously in DM group than that in control group and treatment group (P＜0.05), whereas it was lower in treatment group than that in control group (P ＜ 0.05). The slow wave frequency and amplitude of duodenal smooth muscle cells in DM group were reduced when compared with control and treatment groups (P＜0.01) and both were lower in treatment group than that in control group (P＜0. 01 ). Conclusion The findings indicate that DM mice have gastrointestinal dysmotility and exogenous insulin may improve small intestinal dysmotility in DM mice.     

Matrix metalloproteinase 2 genotype is associated with nonanastomotic biliary strictures after orthotopic liver transplantation

Background: Nonanastomotic biliary strictures (NAS) are a serious complication after orthotopic liver transplantation (OLT). Matrix metalloproteinases (MMPs) are involved in connective tissue remodelling in chronic liver disease and complications after OLT. Aim: To evaluate the relationship between MMP‐2 and MMP‐9 gene polymorphisms and NAS. Methods: MMP‐2 (?1306 C/T) and MMP‐9 (?1562 C/T) gene promoter polymorphisms were analysed in 314 recipient–donor combinations. Serum levels of these MMPs were determined in subgroups of patients as well. NAS were identified with various radiological imaging studies performed within 4 years after OLT and defined as any stricture, dilation or irregularity of the intra‐ or extrahepatic bile ducts of the liver graft followed by an intervention, after exclusion of hepatic artery thrombosis and anastomotic strictures. Results: The average incidence of NAS was 15%. The major clinical risk factor for the development of NAS was PSC in the recipient. The presence of the MMP‐2 CT genotype in donor and/or recipient was associated with a significantly higher incidence of NAS, up to 29% when both donor and recipient had the MMP‐2 CT genotype (P=0.003). In the multivariate analyses, pre‐OLT PSC (hazard ratio 2.1, P=0.02) and MMP‐2 CT genotype (hazard ratio 3.5, P=0.003) were found to be independent risk factors for the development of NAS after OLT. No obvious association was found between NAS and the MMP‐9 genotype and serum levels of the MMPs. Conclusion: MMP‐2 CT genotype of donor and recipient is an independent risk factor, in addition to PSC, for the development of NAS after OLT.     

Type II Collagen Is a Major Component of Bovine Retinal Microvessel Extracellular Matrix

Objective: To determine which interstitial collagen types may be present in bovine retinal microvessel extracellular matrix (ECM). Methods: Dissociated bovine microvessels were treated with detergents and the resultant purified ECM monitored by transmission electron microscopy (TEM). Pepsin-extracted soluble ECM collagens were identified by Western blots. Collagens were further purified by neutral salt precipitation and carboxymethyl cellulose (CMC) chromatography before cyanogen bromide (CNBr) peptide mapping and two-dimensional peptide mapping of CMC-generated fractions. Interstitial collagens were localized by immunofluorescence on frozen sections. Results: Transmission electron microscopy of detergent-purified microvessel ECM demonstrated numerous 10–50-nm collagen fibrils associated with basal laminae regardless of vessel diameter. Western blots showed that soluble ECM collagens were strongly positive for type II, moderate for type III, and weak for type I. CNBr peptide maps and two-dimensional maps of neutral salt and CMC-purified fractions confirmed the presence of type II collagen. Immunofluorescence localized type II collagen in large and small vessels of the retina. Conclusions: Type II collagen is an unexpected major component of bovine microvessel ECM, whereas types I and III are present in minor amounts. Type V collagen is also a substantial ECM component. Accordingly, all four types may contribute to a heterogeneous population of collagenous fibrils identified by TEM in intact isolated retinal microvessel ECM.     

胆汁对兔胃平滑肌条运动的影响

[目的]观察胆汁对兔体外胃平滑肌的影响,并探讨其作用机制.[方法]取兔胃肌条,安置在各恒温灌流肌槽中,并用BL310生物技能实验系统记录胃各部位平滑肌条的收缩活动.[结果]胆汁显著降低兔胃底和胃体纵行肌条张力,减小胃体收缩波平均振幅,并有剂量依赖关系.[结论]胆汁对胃肌条收缩活动具有明显的抑制作用,这种抑制作用部分经由肾上腺素能α受体及前列腺素介导,并有壁内神经节的参与.     

Role of retrograde dilatation in the management of pharyngo-esophageal corrosive strictures

Pharyngo-esophageal corrosive stricture is a complex clinical scenario. If an esophageal opening cannot be found orally through endoscopy, a retrograde approach with a mini-laparotomy and gastrostomy should be attempted. This study primarily aimed at defining the role of preoperative retrograde dilatation of pharyngo-esophageal corrosive strictures. A retrospective analysis of 51 cases of pharyngo-esophageal corrosive strictures identified between 1997-2005 was performed. The demographic details were analyzed. The details of the injury to the pharynx either in isolation or in combination were noted and the management details were recorded. In 21 patients preoperative retrograde dilatation was considered and the technique was successful in 14 (Group I). In seven the technique failed (Group II) and these patients underwent transhiatal resection and gastric pull-through and/or retrosternal pharyngocoloplasty. In Group I patients the postoperative stay was significantly less than in Group II (12 +/- 2.03 days vs. 18 +/- 4.32 days; p = 0.001) Recurrent aspiration, respiratory tract infections, choking sensation and the need for tracheostomy were less frequent in Group I. The overall functional assessment was good in Group I. For treatment of pharyngo-esophageal obstruction, if antegrade dilatation is not possible due to technical reasons, retrograde dilatation is a viable option before opting for organ replacement/bypass procedures. There is no best replacement of the native organ to maintain quality of life.     

氧化型胆固醇对血管平滑肌细胞的损伤作用

目的　以胆固醇为对照 ,观察 3 β 5α 6β 三羟胆固烷 (cholestane 3 β,5α,6β triol)、2 5 羟胆固醇 ( 2 5 hydroxycholesterol)、7 酮胆固醇 ( 7 ketocholesterol)及环氧胆固醇 (cholesterol 5α,6α epoxide)四种氧化型胆固醇对大鼠主动脉平滑肌细胞的损伤作用。方法　取 6～ 10代细胞 ,测定细胞存活率、细胞培养液乳酸脱氢酶活力 ,用电子自旋共振自旋标记检测膜脂流动性和膜蛋白构象。结果　氧化型胆固醇呈时间和剂量依赖性降低细胞存活率、增加培养液乳酸脱氢酶活力 ,以 3 β 5α 6β 三羟胆固烷损伤最重。氧化型胆固醇还使膜脂流动性降低、膜蛋白构象改变及运动减慢。胆固醇除改变膜脂流动性外 ,在相同剂量及相同作用时间的情况下 ,对细胞无损伤作用。结论　氧化型胆固醇对血管平滑肌细胞有损伤作用 ,其中以 3 β 5α 6β 三羟胆固烷损伤最重 ,胆固醇对细胞没有损伤作用。氧化型胆固醇的细胞损伤与膜物理性质改变有关。     

氢溴酸槟榔碱对豚鼠体外胃不同部位肌条作用及其机制

[目的]观察氢溴酸槟榔碱（Ah）对豚鼠体外胃不同部位平滑肌肌条收缩运动的影响，并初步探索其作用机制。[方法]用胃不同部位（6处）平滑肌条置于灌流浴槽，在37℃恒温、通氧和Krebs液灌注条件下，分别记录单独使用Ah和阻断剂孵育后Ah的收缩效应。[结果]①Ah可显著增高各部分体外胃平滑肌条的张力，增大收缩振幅和收缩波曲线下面积，2者均比基础值有显著增高（P〈0．05）。而且其效应强度不同部位有明显差异。纵肌效应：Ah对胃窦纵肌的作用振幅大于胃底、胃体（P〈0．01）；效应曲线下面积大于胃体（P〈0．01）。环肌效应：Ah对胃窦环肌作用振幅大于胃底（P〈0．05）；效应曲线下面积大于胃体和胃底（P〈0．05），对胃体环肌作用的曲线下面积亦大于胃底（P〈0．05）。②阿托品和维拉帕米均能部分阻断Ah的收缩作用，显著降低其振幅（P〈0．01）。[结论]Ah对豚鼠体外胃平滑肌条的收缩活动有明显兴奋作用，推测这种效应部分介导于M-胆碱能受体，L型电压依赖性Ca^2＋通道。     

血管平滑肌细胞凋亡与动脉粥样硬化研究进展

血管平滑肌细胞是构成血管壁的重要组成成分,其凋亡参与了动脉粥样硬化及再狭窄的发生发展,现就最近研究对血管平滑肌细胞凋亡诱导因素、相关基因、及其在动脉粥样硬化发生发展作用作一综述。     

多沙唑嗪对高血压患者动态血管平滑肌细胞NO产生的影响

采用高血压患者的肠系膜动脉进行分离培养,检测细胞培养液中的NO含量.结果多沙唑嗪治疗组的NO含量高于对照组(74.56±4.56μmol/L,42.77±6.76μmol/L,P<0.05).认为多沙唑嗪增加了高血压患者动脉血管平滑肌细胞NO的产生.     

胰岛素对猪主动脉平滑肌细胞的增殖和前列环素合成的影响

以体外培养的猪主动脉平滑肌细胞为实验模型，研究了不同浓度胰岛素对其细胞增殖、前列环素合成的影响。结果显示胰岛素抑制平滑肌细胞的前列环素合成、促进细胞增殖都呈现剂量依赖性，提示高胰岛素血症可能是致动脉粥样样硬化的重要因素之一。