Effects of tachykinin receptor agonists and antagonists on the guinea-pig isolated oesophagus

1. Vagal nerve stimulation of the guinea-pig isolated oesophagus produced a triphasic tetrodotoxin (TTX)-sensitive contractile response. The third phase, which was resistant to ganglion blocking drugs, was selectively abolished by capsaicin, suggesting the involvement of one or more neuropeptides released from afferent neurons. Receptors on cholinergic neurons were subsequently activated because the response was atropine sensitive. Contractile responses resulting from exogenous substance P were abolished by atropine and TTX and enhanced by physostigmine. These findings suggest that the third phase may be mediated by the action of a substance P-like neuropeptide released from sensory nerve endings that subsequently activated cholinergic neurons. 2. The tachykinin receptors in the body of the guinea-pig oesophagus were characterized by determining the relative agonist potencies of natural tachykinins as well as tachykinin receptor-selective analogues. Antagonist affinities were also determined. The results indicated the presence of both NK2 and NK3 receptors. In addition, the effects of a cocktail of peptidase inhibitors (captopril, thiorphan and amastatin) on responses to various tachykinins and synthetic analogues were determined. The results indicate that one or more peptidases are present in this preparation. 3. Experiments using various tachykinin receptor antagonists were performed to determine whether the activation of tachykinin receptors played a role in the mediation of the third phase of the response to vagal nerve stimulation. While this response was unaffected by NK1 and NK2 receptor-selective antagonists, it was only partially inhibited (23%) by the NK3 receptor antagonist SR 142801. Thus, in the guinea-pig oesophagus, it appears that NK3 receptors play only a minor role in mediating a contractile response when afferent neurons are excited by vagal nerve stimulation.     

Expression profile of an operationally-defined neural stem cell clone

Neural stem cells (NSCs) are the most primordial and least committed cells of the nervous system, the cells that exist before regional specification develops. Because immunocytochemically-detectable markers that are sufficiently specific and sensitive to define an NSC have not yet been fully defined, we have taken the strong view that, to be termed a "stem cell" in the nervous system--in contrast to a "progenitor" or "precursor" (whose lineage commitment is further restricted)--a single neuroectodermally-derived cell must fulfill an operational definition that is essentially similar to that used in hematopoiesis. In other words, it must possess the following functional properties: (1) "Multipotency", i.e., the ability to yield mature cells in all three fundamental neural lineages throughout the nervous system--neurons (of all subtypes), astrocytes (of all types), oligodendrocytes--in multiple regional and developmental contexts and in a region and developmental stage-appropriate manner. (2) The ability to populate a developing region and/or repopulate an ablated or degenerated region of the nervous system with appropriate cell types. (3) The ability to be serially transplanted. (4) "Self-renewal", i.e., the ability to produce daughter cells (including new NSCs) with identical properties and potential. Having identified a murine neural cell clone that fulfills this strict operational definition--in contrast to other studies that used less rigorous or non-operational criteria for defining an NSC (e.g., the "neurosphere" assay)--we then examined, by comparing gene expression profiles, the relationship such a cell might have to (a) a multipotent somatic stem cell from another organ system (the hematopoietic stem cell [HSC]); (b) a pluripotent stem cell derived from the inner cell mass and hence without organ assignment (an embryonic stem cell); (c) neural cells isolated and maintained primarily as neurospheres but without having been subjected to the above mentioned operational screen ("CNS-derived neurospheres"). ESCs, HSCs, and operationally-defined NSCs--all of which have been identified not only by markers but by functional assays in their respective systems and whose state of differentiation could be synchronized--shared a large number of genes. Although, as expected, the most stem-like genes were expressed by ESCs, NSCs and HSCs shared a number of genes. CNS-derived neurospheres, on the other hand, expressed fewer "stem-like" genes held in common by the other operationally-defined stem cell populations. Rather they displayed a profile more consistent with differentiated neural cells. (Genes of neural identity were shared with the NSC clone.) Interestingly, when the operationally-defined NSC clone was cultured as a neurosphere (rather than in monolayer), its expression pattern shifted from a "stem-like" pattern towards a more "differentiated" one, suggesting that the neurosphere, without functional validation, may be a poor model for predicting stem cell attributes because it consists of heterogeneous populations of cells, only a small proportion of which are truly "stem-like". Furthermore, when operational definitions are employed, a common set of stem-like genes does emerge across both embryonic and somatic stem cells of various organ systems, including the nervous system.     

Sensory innervation of normal and hypospadiac prepuce: possible implications in hypospadiology

Sensory innervation of the skin influences wound healing through the release of neuropeptides from the nerve endings. The purpose of this study was to investigate the differences in the sensory innervation of the normal and the hypospadiac prepuce. The prepuce from 10 healthy children undergoing routine circumcision and 10 age-matched children undergoing hypospadias repair were submitted for immunohistochemistry, using antibodies against protein gene product (PGP) 9.5, calcitonin gene-related peptide (CGRP), and substance P (SP). The hypospadiac prepuce was found to be hypo-innervated for PGP 9.5 and CGRP positive nerves when compared with the normal prepuce (p<0.05). The number of SP-positive nerves were increased in the hypospadiac prepuce, but not to statistical significance (p=0.06, confidence interval >95%). There may be differences in the sensory innervation of the normal and hypospadiac prepuce. These differences in tissue environment may partly explain the postoperative edema, poor wound healing leading to urethrocutaneous fistula (UF), and increased analgesia requirements in patients undergoing hypospadias surgery.     

Capsaicin facilitates carotid sinus baroreceptor activity in anesthetized rats

AIM: To study the effect of capsaicin on carotid sinus baroreceptor activity (CBA). METHODS: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid sinus baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized rats with perfused isolated carotid sinus. RESULTS: Low-concentration of capsaicin (0.2 μmol/L) had no significant effect on CBA, while perfusion of the isolated carotid sinus with middle-concentration of capsaicin (1 μmol/L) could shift FCCB to the left and upward, with peak slope (PS) increased from (2.47 %±0.14 %)/mmHg to (2.88 %±0.10 %)/mmHg (P<0.05) and peak integral value of carotid sinus nerve discharge (PIV) enhanced from 211 %±5 % to 238 %±6 % (P<0.01). The threshold pressure (TP) and saturation pressure (SP) were significantly decreased from 68.0±1.1 to 62.7±1.0 mmHg (P<0.01) and from 171.0±1.6 to 165.0±0.6 mmHg (P<0.01). By perfusing with high-concentration of capsaicin (5μmol/L), FCCB was shi     

Histamine releasing peptide (HRP) has proinflammatory effects and is present at sites of inflammation

Albumin, the most abundant plasma protein, readily enters sites of inflammation during the period of increased vascular permeability. There it encounters proteases released from mast cells and invading leukocytes which earlier work has shown can act on albumin to liberate the peptide, histamine releasing peptide (HRP), first identified and named by its ability to stimulate histamine release from isolated mast cells. In this report we show that HRP releases histamine from cutaneous mast cells in vivo resulting in increased vascular permeability and persistent edema while in vitro, HRP promotes chemotaxis of leukocytes and enhances macrophage phagocytosis. Moreover, we show that the level of HRP is increased with the induction of an acute cutaneous inflammatory response in rats, that HRP is present at sites of acute and chronic inflammation in humans and that HRP is rapidly degraded by proteases thereby limiting its action to the area of its generation. We suggest that HRP is a pro-inflammatory peptide that helps amplify and perpetuate the inflammatory response. Inhibitors of inflammatory proteases or antagonists that block the action of peptides like HRP may, therefore, be useful in breaking the cycle of inflammation.     

电针"合谷""三阴交"穴促分娩作用机理的实验研究

目的：通过动物实验探讨电针“合谷”“三阴交”穴促分娩的作用机理。方法：选健康成年Wistar大鼠55只,分正常对照组、模型对照组、“合谷”组、“三阴交”组、“合谷”加“三阴交”组。以子宫颈及子宫体组织前列腺素E2(PGEa)、血清及羊水雌二醇(E2)和孕酮(P)为指标。结果：电针“合谷”穴使晚孕大鼠宫体及宫颈组织PGEa、血清E2、羊水中P含量显著升高;电针“三阴交”穴仅使晚孕大鼠羊水中P含量显著升高;同时电针“合谷”“三阴交”穴对本实验所测各项内分泌指标影响不显著。     

加味补阳还五汤对易卒中自发性高血压大鼠血清微量元素的影响

目的观察易卒中自发性高血压大鼠服用加味补阳还五汤后,其血清微量元素锌、铜、铁、硒、锰含量的变化。方法将20只8周龄雄性易卒中自发性高血压大鼠分为两组,用药组(n=10):喂含补阳还五汤的饲料,对照组(n=10):常规饲养;另设同龄WKY大鼠为空白组(n=10)。实验周期3个月,观察指标为:大鼠血清微量元素锌、铜、铁、硒、锰含量。结果空白组锌、锰、硒含量明显高于用药组(P<0.01),用药组又明显高于对照组(P<0.01);而空白组铜含量低于用药组(P<0.05),用药组又低于对照组(P<0.05);血清内铁含量三组间无显著差异(P>0.05)。结论加味补阳还五汤对自发性高血压大鼠血清锌、铜、铁、硒、锰具有一定的调控作用。     

CLINICAL OBSERVATION ON ACUPUNCTURE TREATMENT OF REFRACTORY HICCUP

Since1992,theauthorshavetreated76cases0frefract0ryhiccupinducedbydifferentcauseswithacupunctureatNeiguan(PC6)andG0ngsun(Sp4)P0ints,withsatisfactorythera-peuticeffects,whicharereP0rtedinthefollow-ing.CLINICALDATAOfthe76cases,5lcasesweremaleand25female.Theyoungestwas26yearsoldandtheoldest7lyears;Theshortestduration0fdiseasewas2daysandthelongest4m0nths.Inthepe-riodofacupuncturetreatment,anyChineseandWesternmedicinesweresuspended.THERAPEUTICMETH0DS1.SelectedPOints:Left-rightcrossi…     

低氧急性肺损伤时肺表面活性蛋白的免疫组化研究

目的：探讨急性低氧油酸肺损伤大鼠肺组织中ＳＰ－Ａ和ＳＰ－Ｂ的表达,明确ＳＰ－Ａ和ＳＰ－Ｂ在肺表面活性物质（ＰＳ）中的作用,及其对该系统的影响。方法：采用低氧大鼠油酸肺损伤模型及免疫组化技术,采用己酮可可碱对急性肺损伤进行干预。结果：ＳＰ－Ａ和ＳＰ－Ｂ在肺内的表达主要以肺泡Ⅱ型上皮细胞为对象,ＳＰ－Ｂ的特异性较ＳＰ－Ａ高。肺泡腔和小支气管腔内可见一层免疫阳性物质沉着,肺泡Ⅱ型上皮细胞多位于肺泡隔部和角部并靠近肺泡腔。己酮可可碱可使ＳＰ－Ａ蛋白表达增加。结论：ＳＰ－Ａ和ＳＰ－Ｂ在肺内的表达主要以肺泡Ⅱ型上皮细胞为对象,气道上皮和血管内皮以及间质细胞均未见明显的表达,ＳＰ－Ｂ的特异性较ＳＰ－Ａ高。急性低氧油酸肺损伤时,肺组织ＳＰ－Ａ和ＳＰ－Ｂ免疫组化显示肺泡Ⅱ型上皮细胞的表达明显减弱。己酮可可碱可使ＳＰ－Ａ蛋白表达增加。