Variability in the muscle composition of rat esophagus and neural pathway of lower esophageal sphincter relaxation

Several studies from our laboratory show that axial stretch of the lower esophageal sphincter (LES) in an oral direction causes neurally mediated LES relaxation. Under physiological conditions, axial stretch of the LES is caused by longitudinal muscle contraction (LMC) of the esophagus. Because longitudinal muscle is composed of skeletal muscle in mice, vagal-induced LMC and LES relaxation are both blocked by pancuronium. We conducted studies in rats (thought to have skeletal muscle esophagus) to determine if vagus nerve-mediated LES relaxation is also blocked by pancuronium. LMC-mediated axial stretch on the LES was monitored using piezoelectric crystals. LES and esophageal pressures were monitored with a 2.5-Fr solid-state pressure transducer catheter. Following bilateral cervical vagotomy, the vagus nerve was stimulated electrically. LES, along with the esophagus, was harvested after in vivo experiments and immunostained for smooth muscle (smooth muscle α-actin) and skeletal muscle (fast myosin heavy chain). Vagus nerve-stimulated LES relaxation and esophageal LMC were reduced in a dose-dependent fashion and completely abolished by pancuronium (96 μg/kg) in six rats (group 1). On the other hand, in seven rats, LES relaxation and LMC were only blocked completely by a combination of pancuronium (group 2) and hexamethonium. Immunostaining revealed that the longitudinal muscle layer was composed of predominantly skeletal muscle in the group 1 rats. On the other hand, the longitudinal muscle layer of group 2 rats contained a significant amount of smooth muscle (P < 0.05). Our study shows tight coupling between axial stretch on the LES and relaxation of the LES, which suggests a cause and effect relationship between the two. We propose that the vagus nerve fibers that cause LMC induce LES relaxation through the stretch-sensitive activation of inhibitory motor neurons.     

Comparison of LES of steady transitional flow in an idealized stenosed axisymmetric artery model with a RANS transitional model

In this study, two different turbulence methodologies are investigated to predict transitional flow in a 75% stenosed axisymmetric experimental arterial model and in a slightly modified version of the model with an eccentric stenosis. Large eddy simulation (LES) and Reynolds-averaged Navier-Stokes (RANS) methods were applied; in the LES simulations eddy viscosity subgrid-scale models were employed (basic and dynamic Smagorinsky) while the RANS method involved the correlation-based transitional version of the hybrid k-ε/k-ω flow model. The RANS simulations used 410,000 and 820,000 element meshes for the axisymmetric and eccentric stenoses, respectively, with y(+) less than 2 viscous wall units for the boundary elements, while the LES used 1,200,000 elements with y(+) less than 1. Implicit filtering was used for LES, giving an overlap between the resolved and modeled eddies, ensuring accurate treatment of near wall turbulence structures. Flow analysis was carried out in terms of vorticity and eddy viscosity magnitudes, velocity, and turbulence intensity profiles and the results were compared both with established experimental data and with available direct numerical simulations (DNSs) from the literature. The simulation results demonstrated that the dynamic Smagorinsky LES and RANS transitional model predicted fairly comparable velocity and turbulence intensity profiles with the experimental data, although the dynamic Smagorinsky model gave the best overall agreement. The present study demonstrated the power of LES methods, although they were computationally more costly, and added further evidence of the promise of the RANS transition model used here, previously tested in pulsatile flow on a similar model. Both dynamic Smagorinsky LES and the RANS model captured the complex transition phenomena under physiological Reynolds numbers in steady flow, including separation and reattachment. In this respect, LES with dynamic Smagorinsky appeared more successful than DNS in replicating the axisymmetric experimental results, although inflow conditions, which are subject to caveats, may have differed. For the eccentric stenosis, LES with Smagorinsky coefficient of 0.13 gave the closest agreement with DNS despite the known shortcomings of fixed coefficients. The relaminarization as the flow escaped the influence of the stenosis was amply demonstrated in the simulations, graphically so in the case of LES.     

Patterns of esophageal inhibition during swallowing,pharyngeal stimulation,and transient LES relaxation. Lower esophageal sphincter

Lower esophageal sphincter (LES) relaxation and esophageal body inhibition co-occur during esophageal peristalsis but not necessarily during pharyngeal stimulation or transient LES relaxation (tLESR). This study examined these relationships and the impact on reflux. Nine young volunteers were studied. An artificial high-pressure zone (HPZ) was established, and pH was recorded 8 and 5 cm proximal to the LES. Pharyngeal stimulation was by water injection and gastric distension with liquid or gas. Peristalsis, pharyngeal stimulation, and spontaneous events were recorded. Swallowing relaxed the LES in 100% of trials (the HPZ in 80%) and caused no reflux. Pharyngeal stimulation relaxed the LES in two-thirds of trials, had no effect on the HPZ, and caused no reflux. Gastric distension was associated with 117 tLESRs, 48% with acid reflux, and 32% with gas reflux; there was no effect on the HPZ. We conclude that LES relaxation is a necessary but not sufficient condition for reflux. LES relaxation and esophageal body inhibition are independent events that may be concurrent (swallowing) or dissociated (tLESR).     

植物叶经济谱的研究进展

叶经济谱(leaf economics spectrum)概念自提出以来, 已受到广泛关注。它第一次在全球尺度上定量分析植物功能性状及其关系, 从而量化和概括权衡策略(trade-off)的内涵和变化规律, 具有重要的理论价值, 为后续植物性状的相关研究提供借鉴。该文综合评述了叶经济谱的概念、内容和相关检验性或异议性观点, 探讨叶经济谱的形成机制与动力, 并从多角度、多方面概述叶经济谱理论的应用及扩展性研究, 最后指出我国叶经济谱研究现状的不足, 并对国内外叶经济谱理论的发展进行展望, 强调共建共享全球基础数据库的重要性。     

The Impact of a Diabetes Local Enhanced Service on Quality Outcome Framework Diabetes Outcomes

Background

The rising challenge of diabetes requires novel service delivery approaches. In the UK, Local Enhanced Services (LES) have been commissioned for diabetes. Health professionals from general practices (GPs) who signed up to LES were given additional training (and a monetary incentive) to improve management of patients with diabetes. All practices in the PCT were invited to the LES initiative, which ensured avoiding selection bias. The aim of the study was to examine the impact of LES in terms of diabetes Quality Outcome Framework (QOF) indicators: DM23(glycaemia), DM17(lipid) and DM12(blood pressure; BP).

Methods

QOF diabetes indicators were examined using data from 76 general practices for 2009–2010 in a large primary care trust area in Birmingham, UK. Data were extracted from Quality Management Analysis System. The primary outcome was a difference in achievement of QOF indicators between LES and NLES practices. A secondary outcome was the difference between LES and non-LES practices for hospital first and follow-up appointments.

Results

We did not find any difference for DM12(BP) and DM17(lipid) outcomes between LES and NLES practices. However, LES practices were more likely to achieve the DM23(glycaemia) outcome (estimated odds 1.459;95% CI:1.378-1.544; P=0.0001). The probability of achieving satisfactory level of DM23(glycaemia) increased by almost 10% when GPs belonged to LES groups compared with GPs in NLES group. LES practices were less likely to refer patients to secondary care.

Conclusion

Overall, LES practices performed better in the achievement of DM23(glycaemia) and also referred fewer patients to hospital, thereby meeting their objectives. This suggests that the LES approach is beneficial and needs to be further explored in order to ascertain whether the impact exerted was due to LES.     

Regional differences in L-type Ca2+ channel expression in feline lower esophageal sphincter

In humans and cats, muscle from the lower esophageal sphincter (LES) circular region exhibits greater spontaneous tone than LES sling muscle, whereas the sling muscle is much more responsive to cholinergic stimulation. Despite physiological and pharmacological evidence for the presence of L-type Ca2+ channel current (ICa,L) activity in LES circular muscle, the identity of this channel has not been demonstrated biochemically or electrophysiologically fingerprinted. Furthermore, there is no information on the channel's presence and role in the sling region of the LES. We hypothesized that regional differences in the expression of ICa,L between LES circular and sling muscles, if present, could contribute to the functional asymmetry observed within the LES. ICa,L expression was compared between circular and sling regions of the LES by Western blot analysis. The patch-clamp technique was used to study ICa,L. Muscle strip studies assessed ICa,L contribution to contractile activity. We found both protein expression of ICa,L and ICa,L density to be greater in LES circular muscle than sling muscle. ICa,L voltage- and time-dependent activation and inactivation curves were similar in cells from both regions. ICa,L blockade with nifedipine inhibited spontaneous tone and ACh-induced contractions only in circular muscle but was able to abolish depolarization (KCl)-induced contractions in both sling and circular muscles. In contrast, La3+ inhibited tone and ACh-induced contractions in muscles from both regions. Therefore, regional myogenic differences in ICa,L expression within the LES circular and sling muscle exist and provide one explanation for the differential contribution of sling and circular muscle to LES contractility.     

Localization and inhibitory actions of galanin at the feline lower esophageal sphincter

Intrinsic reflexes of the lower esophageal sphincter (LES) are mediated by specific arrangements of excitatory and inhibitory nerves. We have previously described an excitatory reflex at the feline LES mediated by a bombesin-like peptide (BN) which causes release of substance P (SP) to directly contract the LES. Galanin is a neurotransmitter in the enteric nervous system which colocalizes in neurons containing vasoactive intestinal peptide (VIP). The aims of this study were to determine: (1) the distribution of galanin at the feline LES; (2) the effect of galanin on basal LES tone; (3) the effect of galanin on agonist-induced LES contractions by BN, SP and bethanechol; and (4) the effect of galanin on LES relaxation induced by esophageal distension and exogenous VIP. Galanin-like immunoreactivity (galanin-LI) was localized in neurons that were widely distributed throughout the LES and adjacent organs. Galanin-LI was most abundant in the circular muscle, muscularis mucosa and myenteric plexus of the LES. In anesthetized cats, intra-arterial galanin had no effect on basal LES pressure in a dose range of 10⁻¹¹ to 10⁻⁶ g/kg. Galanin (5 10⁻⁷ g/kg) reduced the LES contractile response to SP by 65 ± 8% (P = 0.0001). This galanin-mediated inhibition of SP was not blocked by tetrodotoxin. Galanin similarly decreased the LES contractile response to BN (63 ± 7%, P = 0.005) and bethanechol (55 ± 17%, P = 0.012). Galanin had no effect on the LES relaxation induced by esophageal distension or exogenous VIP. We conclude: (1) galanin-LI is present in neurons at the feline LES; (2) galanin has no effect on basal sphincter tone, but inhibits contractions of the LES by both direct and indirect agonists; and (3) galanin does not effect the LES relaxation induced by esophageal distension or VIP.     

The impact of continuous positive airway pressure on the lower esophageal sphincter

The lower esophageal sphincter (LES) is the primary barrier to gastroesophageal reflux. Reflux is associated with periods of LES relaxation, as occurs during swallowing. Continuous positive airway pressure (CPAP) has been shown to reduce reflux in individuals with and without sleep apnea, by an unknown mechanism. The aim of this study was to determine the effect of CPAP on swallow-induced LES relaxation. Measurements were made in 10 healthy, awake, supine individuals. Esophageal (Pes), LES (Ples), gastric (Pg), and barrier pressure to reflux (Pb = Ples - Pg) were recorded using a sleeve catheter during five swallows of 5 ml of water. This was repeated at four levels of CPAP (0, 5, 10, and 15 cmH(2)O). Pressures were measured during quiet breathing and during the LES relaxation associated with a swallow. Duration of LES relaxation was also recorded. During quiet breathing, CPAP significantly increased end-expiratory Pes, Ples, Pg, and Pb (P < 0.05). The increase in Pb was due to a disproportionate increase in Ples compared with Pg (P < 0.05). During a swallow, CPAP increased nadir Ples, Pg, and Pb and decreased the duration of LES relaxation (4.1 s with 0-cmH(2)O CPAP to 1.6 s on 15-cmH(2)O CPAP, P < 0.001). Pb increased with CPAP by virtue of a disproportionate increase in Ples compared with Pg. This may be due to either reflex activation of LES smooth muscle, or nonspecific transmission of pressure to the LES. The findings suggest CPAP may make the LES less susceptible to reflux by increasing Pb and decreasing the duration of LES relaxation.     

Indirect immunofluorescence (IFA) on kinetoplasts of Trypanosoma theileri for serological diagnosis of systemic lupus erythematosus (LES) in the dog

An indirect immunofluorescence technique was developed to detect antibodies to ds-DNA in a dog affected by Systemic Lupus Erythematosus (LES). The assay was based upon the use of the antigen substrate Trypanosoma theileri, isolated from samples of bovine blood and maintained in culture tubes. Slides were prepared by the drop method and maintained at -20 degrees C until used. This T. theileri immunofluorescence test, evaluated with positive and discriminant results in a previous study on human sera affected by LES, was used for the first time in the diagnosis of canine LES. The results indicate that T. theileri IFA is specific and reliable.     

Somatostatin selectively inhibits excitatory contractile pathways of the feline lower esophageal sphincter.

Intrinsic reflexes of the feline lower esophageal sphincter (LES) have been shown to be mediated by specific arrangements of excitatory peptidergic interneurons. Inhibition of intrinsic reflexes may also be mediated by neuropeptides. The specific aims of this study were: (1) to examine the effect of somatostatin (SOM) and vasoactive intestinal peptide (VIP) on basal LES tone, and (2) to determine if these transmitters exert selective inhibitory effects on excitatory contractile pathways. Intraluminal pressures were recorded from the LES, esophagus and fundus by a fixed perfused catheter assembly in anesthetized cats. Peptides were administered via the left gastric artery. SOM had no effect on basal LES pressure with doses ranging from 10(-9) to 10(-5) g/kg. VIP induced a dose-dependent inhibition of basal LES pressure. The maximal effective dose of VIP, 10(-6) g/kg, completely inhibited basal LES pressure (34.7 +/- 6.8 to 1.0 +/- 0.6 mmHg, P less than 0.001). We have previously shown that bombesin (BN) but not substance P (SP) or bethanechol contracts the LES via tetrodotoxin-sensitive pathways. BN at the D50 (5.10(-8) g/kg) increased LES pressure by 32.1 +/- 3.6 mmHg. SOM (10(-5) g/kg) decreased this BN response to 19.2 +/- 5.0 mmHg, P less than 0.05. In contrast, while the D50 of SP (5.10(-8) g/kg) gave a similar increase in LES pressure, 28.8 +/- 5.1 mmHg, this effect was not altered by SOM (23.8 +/- 6.7 mmHg, P greater than 0.10). SOM also had no effect on bethanechol-induced LES contractions (P greater than 0.10). VIP (10(-6) g/kg) totally inhibited the LES response to the D50 of BN, SP, and bethanechol. A submaximal dose of VIP (10(-7) g/kg) partially inhibited the contractile response of all three. Conclusions: (1) VIP, but not SOM, inhibits basal LES tone. (2) SOM selectively inhibits BN but not SP- or bethanechol-induced LES contraction. (3) VIP inhibits BN, SP and bethanechol-induced LES contractions. These studies suggest that somatostatin can selectively inhibit excitatory interneurons at the LES.     

Role of cGMP as a mediator of nerve-induced motor functions of the opossum esophagus

Stimulation of esophageal nerves produces biphasic relaxation of the lower esophageal sphincter (LES) and an off response of circular esophageal muscle. Previously, we proposed that cGMP mediates nerve-induced hyperpolarization of circular LES muscle but not LES relaxation. These experiments explore whether cGMP mediates LES relaxation or the off response. Strips of muscle from the opossum esophagus and LES were connected to force-displacement transducers, placed in tissue baths containing oxygenated Krebs solution at 37 degrees C, and stimulated by an electrical field. 1H-[1,2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of guanylyl cyclase, antagonized the off response, shortened its latency, and blocked the first phase of LES relaxation. ODQ also antagonized LES relaxation by exogenous nitric oxide (NO) but not relaxations by vasoactive intestinal polypeptide (VIP). Part of the nerve-induced LES relaxation and the off response appear to be mediated by the second messenger cGMP. These studies indicate that VIP-induced LES relaxation is not mediated by cGMP and therefore do not support the hypothesis that VIP produces LES relaxation by causing the generation of NO.     

Studies of abnormalities of the lower esophageal sphincter during esophageal emptying based on a fully coupled bolus–esophageal–gastric model

The aim of this work was to develop a fully coupled bolus–esophageal–gastric model based on the immersed boundary–finite element method to study the process of esophageal emptying across the esophagogastric junction (EGJ). The model included an esophageal segment, an ellipsoid-shaped stomach, a bolus, and a simple model of the passive and active sphincteric functions of the lower esophageal sphincter (LES). We conducted three sets of case studies: (1) the effect of a non-relaxing LES; (2) the influence of the tissue anisotropy in the form of asymmetrical right- and left-sided compliance of the LES segment; and (3) the influence of LES and gastric wall stiffness on bulge formation of the distal esophageal wall. We found that a non-relaxing LES caused sustained high wall stress along the LES segment and obstruction of bolus emptying. From the simulations of tissue anisotropy, we found that the weaker side (i.e., more compliant) of the LES segment sustained greater deformation, greater wall shear stress, and a greater high-pressure load during bolus transit. In the third set of studies, we found that a right-sided bulge in the esophageal wall tends to develop during esophageal emptying when LES stiffness was decreased or gastric wall stiffness was increased. Hence, the bulge may be partly due to the asymmetric configuration of the gastric wall with respect to the esophageal tube. Together, the observations from these simulations provide insight into the genesis of epiphrenic diverticula, a complication observed with esophageal motility disorders. Future work, with additional layers of complexity to the model, will delve into the mechanics of gastroesophageal reflux and the effects of hiatus hernia on EGJ function.     

Pressure morphology of the relaxed lower esophageal sphincter: the formation and collapse of the phrenic ampulla

This study aimed to apply novel high-resolution manometry with eight-sector radial pressure resolution (3D-HRM technology) to resolve the deglutitive pressure morphology at the esophagogastric junction (EGJ) before, during, and after bolus transit. A hybrid HRM assembly, including a 9-cm-long 3D-HRM array, was used to record EGJ pressure morphology in 15 normal subjects. Concurrent videofluoroscopy was used to relate bolus movement to pressure morphology and EGJ anatomy, aided by an endoclip marking the squamocolumnar junction (SCJ). The contractile deceleration point (CDP) marked the time at which luminal clearance slowed to 1.1 cm/s and the location (4 cm proximal to the elevated SCJ) at which peristalsis terminated. The phrenic ampulla spanned from the CDP to the SCJ. The subsequent radial and axial collapse of the ampulla coincided with the reconstitution of the effaced and elongated lower esophageal sphincter (LES). Following ampullary emptying, the stretched LES (maximum length 4.0 cm) progressively collapsed to its baseline length of 1.9 cm (P < 0.001). The phrenic ampulla is a transient structure comprised of the stretched, effaced, and axially displaced LES that serves as a "yield zone" to facilitate bolus transfer to the stomach. During ampullary emptying, the LES circular muscle contracts, and longitudinal muscle shortens while that of the adjacent esophagus reelongates. The likely LES elongation with the formation of the ampulla and shortening to its native length after ampullary emptying suggest that reduction in the resting tone of the longitudinal muscle within the LES segment is a previously unrecognized component of LES relaxation.     

Role of endogenous prostaglandins in regulating the tone of opossum lower esophageal sphincter in vivo.

The role of prostaglandins in maintenance of basal myogenic tone of the lower esophageal sphincter (LES) of opossum has been studied in vivo. Intra-arterial infusion of arachidonic acid decreased LES tone, and this was inhibited by intravenous indomethacin (IDM) or intra-arterial 5,8,11,14-eicosatetraynoic acid (ETA). Alone these drugs did not reduce LES tone except transiently. In addition they did not affect relaxation of the LES to distention of a balloon located proximal to it or inhibit the "off" contractions of esophageal body and LES pressure which followed balloon deflation. Spontaneous oscillations of LES pressure were increased with IDM. Thus prostaglandin synthesis plays no essential role in maintenance of resting LES tone or in functioning of non-adrenergic inhibitory nerves in the esophagus in vivo. Endogenous inhibitory prostaglandins might reduce LES tone if synthesized in increased amounts.     

Axial stretch: A novel mechanism of the lower esophageal sphincter relaxation

Swallow and esophageal distension-induced relaxations of the lower esophageal sphincter (LES) are associated with an orad movement of the LES because of a concurrent esophageal longitudinal muscle contraction. We hypothesized that the esophageal longitudinal muscle contraction induces a cranially directed mechanical stretch on the LES and therefore studied the effects of a mechanical stretch on the LES pressure. In adult opossums, a silicon tube was placed via mouth into the esophagus and laparotomy was performed. Two needles with silk sutures were passed, 90 degrees apart, through the esophageal walls and silicon tube, 2 cm above the LES. The tube was withdrawn, and one end of each of the four sutures was anchored to the esophageal wall and the other end exited through the mouth to exert graded cranially directed stretch on the LES by using pulley and weights. A cranially directed stretch caused LES relaxation, and with the cessation of stretch there was recovery of the LES pressure. The degree an d duration of LES relaxation increased with the weight and the duration of stretch, respectively. The mean LES relaxation in all animals was 77.7 +/- 4.7%. The required weight to induce maximal LES relaxation differed in animals (714 +/- 348 g). N(G)-nitro-L-arginine, a nitric oxide inhibitor, blocked the axial stretch-induced LES relaxation almost completely (from 78 to 19%). Our data support the presence of an axial stretch-activated inhibitory mechanism in the LES. The role of axial stretch in the LES relaxation induced by swallow and esophageal distension requires further investigation.     

植物功能性状权衡关系的研究进展

植物功能性状权衡关系反映了植物在资源获取与分配中采取的不同策略, 是近年来生态学研究的一个热点问题。该综述从研究范围、叶性状、器官和植物类群4个方面入手, 简要介绍植物功能性状关系研究在近10余年是如何在叶经济谱(LES)的基础上逐渐扩展和深入的。1)相关研究拓展到全球更多极端环境与特殊气候地区, 发现在不同的气候环境条件下, 植物叶片功能性状关系相对稳定, 植物种内的功能性状关系已被证实与LES相似; 2)功能性状网络从最初的6个经济性状扩展到叶片的分解、燃烧和水力等性状, 发现叶片的分解速率和可燃性均与叶片形态性状、养分含量等显著相关, 但叶片水力性状与经济性状的关系则取决于所研究的物种及生存环境的水分条件; 3)研究对象从植物叶片拓展到了根、茎、花、种子及植株整体, 叶片的比叶质量与茎的木质密度、种子大小相耦合, 但叶片形态性状与根和花的相关性状却无显著相关关系, 证明这些器官可能是独立进化的; 4) LES可以很好地解释特殊维管植物的生存适应策略: 入侵植物具有较高的资源利用效率和更快的相对生长速率, 在LES中处于“低投入-快速回报”的一端; 食虫植物的叶片特化为捕食器官, 光合作用及生长速率相对较低, 居于LES “高投入-缓慢回报”的另一端, 此外, 无论是最古老的种子植物苏铁属(Cycas)植物, 或是蕨类和变水植物(苔藓和地衣), 其功能性状关系都与LES大致相同。该文梳理了功能性状关系研究的进展脉络, 提出了一些建议, 期望为未来植物功能性状关系研究的选题和发展提供一些参考。     

Regional functional specialization and inhibitory nitrergic and nonnitrergic coneurotransmission in the human esophagus

The aim of this study was to explore the myenteric mechanisms of control of human esophageal motility and the effect of nitrergic and nonnitrergic neurotransmitters. Human circular esophageal strips were studied in organ baths and with microelectrodes. Responses following electrical field stimulation (EFS) of enteric motoneurons (EMNs) or through nicotinic acetylcholine receptors were compared in the esophageal body (EB) and in clasp and sling regions in the lower esophageal sphincter (LES). In clasp LES strips: 1) sodium nitroprusside (1 nM to 100 μM), adenosine-5'-[β-thio]diphosphate trilithium salt (1-100 μM), and vasoactive intestinal peptide (1 nM to 1 μM) caused a relaxation; 2) 1 mM N(ω)-nitro-L-arginine (L-NNA) shifted the EFS "on"-relaxation to an "off"-relaxation, partly antagonized by 10 μM 2'-deoxy-N(6)-methyladenosine 3',5'-bisphosphate tetrasodium salt (MRS2179) or 10 U/ml α-chymotrypsin; and 3) nicotine-relaxation (100 μM) was mainly antagonized by L-NNA, and only partly by MRS2179 or α-chymotrypsin. In sling LES fibers, EFS and nicotine relaxation was abolished by L-NNA. In the EB, L-NNA blocked the latency period, and MRS2179 reduced "off"-contraction. The amplitude of cholinergic contraction decreased from the EB to both LES sides. EFS induced a monophasic inhibitory junction potential in clasp, sling, and EB fibers abolished by L-NNA. Our study shows a regional specialization to stimulation of EMNs in the human esophagus, with stronger inhibitory responses in clasp LES fibers and stronger cholinergic excitatory responses in the EB. Inhibitory responses are mainly triggered by nitrergic EMNs mediating the inhibitory junction potentials in the LES and EB, EFS on-relaxation in clasp and sling LES sides, and latency in the EB. We also found a minor role for purines (through P2Y(1) receptors) and vasoactive intestinal peptide-mediating part of nonnitrergic clasp LES relaxation.     

Prostaglandin E1 effects on resting and cholinergically stimulated lower esophageal sphincter pressure in cats

Intraluminal esophageal manometry with a sleeve catheter was used to compare the magnitude of decrease in lower esophageal sphincter (LES) pressure produced by an arterial or venous infusion of prostaglandin E1 in cats. Arterial PGE1 produced significantly lower LES pressures than venous PGE1 (p less than 0.05). Maximal decrease of 75% in basal LES pressure occurred with an associated 15% decrease in systolic blood pressure. The site of action of PGE1 in producing LES hypotension was studied by injection of either edrophonium, or bethanechol during the maximal PGE1 effect. Bethanechol, which acts directly on sphincteric smooth muscle, produced an increase in LES pressure during both saline and PGE1 infusion, while the increases in LES pressure seen with edrophonium during saline infusion were blocked during the PGE1 infusion. From these studies, we conclude that PGE1 produces LES hypotension in the cat by an inhibitory effect on the cholinergic pathway responsible for maintaining LES tone. These studies pharmacologically reproduce the LES pressure abnormality previously reported in the cat during acid-induced esophagitis and support the hypothesis that PGE1 may be involved in the pathogenesis of acute acid-induced lower esophageal sphincter abnormalities.     

Phylogenetic structural equation modelling reveals no need for an ‘origin’ of the leaf economics spectrum

The leaf economics spectrum (LES) is a prominent ecophysiological paradigm that describes global variation in leaf physiology across plant ecological strategies using a handful of key traits. Nearly a decade ago, Shipley et al. (2006) used structural equation modelling to explore the causal functional relationships among LES traits that give rise to their strong global covariation. They concluded that an unmeasured trait drives LES covariation, sparking efforts to identify the latent physiological trait underlying the ‘origin’ of the LES. Here, we use newly developed phylogenetic structural equation modelling approaches to reassess these conclusions using both global LES data as well as data collected across scales in the genus Helianthus. For global LES data, accounting for phylogenetic non‐independence indicates that no additional unmeasured traits are required to explain LES covariation. Across datasets in Helianthus, trait relationships are highly variable, indicating that global‐scale models may poorly describe LES covariation at non‐global scales.     

Role of endogenous prostaglandins in regulating the tone of opossum lower esophageal sphincter in vivo

The role of prostaglandins in maintenance of basal myogenic tone of the lower esophageal sphincter (LES) of opossum has been studied $\text{in vivo}$. Intra-arterial infusion of arachidonic acid decreased LES tone, and this was inhibited by intravenous indomethacin (IDM) or intra-arterial 5,8,11,14-eicosatetraynoic acid (ETA). Alone these drugs did not reduce LES tone except transiently. In addition they did not affect relaxation of the LES to distention of a balloon located proximal to it or inhibit the “off” contractions of esophageal body and LES pressure which followed balloon deflation. Spontaneous oscillations of LES pressure were increased with IDM. Thus prostaglandin synthesis plays no essential role in maintenance of resting LES tone or in functioning of non-adrenergic inhibitory nerves in the esophagus $\text{in vivo}$. Endogenous inhibitory prostaglandins might reduce LES tone if synthesized in increased amounts.