Oligoneuronal Hypoganglionosis in Patients with Idiopathic Slow-Transit Constipation

PURPOSE: Several alterations of the enteric nervous system have been described as an underlying neuropathologic correlate in patients with idiopathic slow-transit constipation. To obtain comprehensive data on the structural components of the intramural nerve plexus, the colonic enteric nervous system was investigated in patients with slow-transit constipation and compared with controls by means of a quantitative morphometric analysis. METHODS: Resected specimens were obtained from ten patients with slow-transit constipation and ten controls (nonobstructive neoplasias) and processed for immunohistochemistry with the neuronal marker Protein Gene Product 9.5. The morphometric analysis was performed separately for the myenteric plexus and submucous plexus compartments and included the quantification of ganglia, neurons, glial cells, and nerve fibers. RESULTS: In patients with slow-transit constipation, the total ganglionic area and neuronal number per intestinal length as well as the mean neuron count per ganglion were significantly decreased within the myenteric plexus and external submucous plexus. The ratio of glial cells to neurons was significantly increased in myenteric ganglia but not in submucous ganglia. On statistical analysis, the histopathologic criteria (submucous giant ganglia and hypertrophic nerve fibers) of intestinal neuronal dysplasia previously described in patients with slow-transit constipation were not completely fulfilled. CONCLUSION: The colonic motor dysfunction in slow-transit constipation is associated with quantitative alterations of the enteric nervous system. The underlying defect is characterized morphologically by oligoneuronal hypoganglionosis. Because the neuropathologic alterations primarily affect the myenteric plexus and external submucous plexus, superficial submucous biopsies are not suitable to detect these innervational disorders.     

应激对大鼠结肠神经系统nNOS表达的影响

目的:探讨应激对大鼠结肠神经系统nNOS表达的影响. 方法:SD大鼠30只随机分为对照组,应激组和L-NAME 组,采用水浸-束缚应激(WRS)动物模型,用免疫组织化学ABC法检测nNOS在大鼠结肠黏膜下神经丛和肌间神经丛的表达,应用计算机图像分析系统对其表达进行定量分析．结果:与对照组比较,应激组黏膜下神经丛和肌间神经丛的nNOS阳性神经元的灰度值明显减少(P=0．02或P =0．005),阳性神经元细胞数的平均密度增加(P=0．04 或P=0．01),表达增强,且在黏膜上皮细胞、固有层淋巴细胞也有nNOS表达．L-NAME组黏膜下神经丛和肌间神经丛的nNOS阳性神经元的灰度值较应激组增加 (P=0．04),平均密度下降(P=0．04或P=0．03),表达减弱,而与对照组比较均无明显差异(P>0．05)．结论:应激可引起大鼠结肠神经系统nNOS表达增强, 提示一氧化氮(NO)在应激所致的结肠功能失调中可能起重要作用．     

慢传输型便秘结肠肌间神经丛超微结构改变

目的　慢传输型便秘（ＳＴＣ） 病因不清、症状顽固、临床处理较困难． 进一步探讨其发生和发展的病理学基础．方法　应用电镜技术对１４ 例ＳＴＣ 患者和１１ 例非梗阻性直肠癌患者经手术切除的乙状结肠标本进行了对照研究．结果　与对照组相比，ＳＴＣ 患者结肠肌间神经丛的超微病理改变表现为：神经元及其突起有十分明显的退行性变，轴突及树突空化呈网格状结构，胞质内出现空泡及脂褐素等；轴突末端膨体及突触前区内突触小泡含量明显减少，大部分突触小泡出现空化．结论　ＳＴＣ 患者结肠肌间神经丛有明显的神经病理学改变，存在递质耗竭或递质合成、传输障碍等现象，它是ＳＴＣ 患者肠道传输减慢的超微病理基础． 这种改变可能与ＳＴＣ 患者长期滥用接触性泻剂有关．     

Notable postnatal alterations in the myenteric plexus of normal human bowel

BACKGROUND: Nitric oxide is the most important transmitter in non-adrenergic non-cholinergic nerves in the human gastrointestinal tract. Impaired nitrergic innervation has been described in Hirschsprung's disease, hypertrophic pyloric stenosis, and intestinal neuronal dysplasia (IND). Recent findings indicate that hyperganglionosis, one of the major criteria of IND, is age dependent. However, information is scanty regarding the neurone density in normal human bowel in the paediatric age group. AIMS: To determine neurone density, morphology, and nitric oxide synthase distribution of the normal myenteric plexus at different ages during infancy and childhood. METHODS: Specimens were obtained from small bowel and colon in 20 children, aged one day to 15 years, at postmortem examination. Whole mount preparations were made of the myenteric plexus, which were subsequently stained using NADPH diaphorase histochemistry (identical to nitric oxide synthase) and cuprolinic blue (a general neuronal marker). The morphology of the myenteric plexus was described and the neurone density estimated. RESULTS: The myenteric plexus meshwork becomes less dense during the first years of life. The density of ganglion cells in the myenteric plexus decreases significantly with age during the first three to four years of life. The NADPH diaphorase positive (nitrergic) subpopulation represents about 34% of all neurones in the myenteric plexus. CONCLUSIONS: The notable decrease in neurone density in the myenteric plexus during the first years of life indicates that development is still an ongoing process in the postnatal enteric nervous system. Applied to the clinical situation, this implies that interpretation of enteric nervous system pathology is dependent on the age of the patient.     

Effect of chagas' disease on nitric oxide-containing neurons in severely affected and unaffected intestine

PURPOSE: The pathophysiology of Chagas' disease is incompletely understood. Neuronal nitric oxide has been cited as a candidate neurotransmitter responsible for relaxation of the internal anal sphincter. Neuronal nicotinamide adenine dinucleotide phosphate diaphorase can be used as a marker for neuronal nitric oxide synthase. This study was designed to examine the alterations of the nitric oxidecontaining neurons in the enteric nervous system of the colon of patients who underwent resections for advanced megacolon and to compare these specimens with small-bowel specimens from the same patients and with specimens from control subjects. METHODS: Specimens from resected rectum and extramucosal small-bowel biopsy specimens from 11 patients with Chagas megacolon but no apparent small-bowel clinical involvement were compared with the uninvolved colon and jejunum of 10 control patients with colon cancer. Tissues were fixed in Zamboni solution and evaluated by histochemistry for nicotinamide adenine dinucleotide phosphate diaphorase-containing neurons. Reactivity was evaluated on a 0 to 4 scale in the longitudinal muscle, myenteric plexus, circular muscle, submucosal plexus, and mucosa. RESULTS: Specimens from control patients showed well-stained myenteric and submucosal neurons and an abundant network of terminal nerve fibers in the muscle layers. Chagasic specimens had decreased staining in all layers of the gut. Overall there was a statistically significant decrease in nicotinamide adenine dinucleotide phosphate diaphorase-containing neurons. Biopsy specimens from clinically uninvolved small bowel of patients with Chagas' disease also showed decreased reactivity, but to a lesser degree. CONCLUSIONS: Nicotinamide adenine dinucleotide phosphate diaphorase activity is decreased in patients with advanced megacolon. The alterations are more relevant in the myenteric plexus and the circular muscle. Reactivity is also diminished in the clinically uninvolved small bowel, but to a lesser extent.     

Immunohistochemical study of the colonic muscle and innervation in idiopathic chronic constipation

PURPOSE: This study was designed to investigate neural and muscular features of the colonic wall in patients with severe idiopathic constipation. METHODS: By using quantitative immunohistochemistry, resected specimens from 14 patients with idiopathic chronic constipation and 17 nonobstructed cancer controls were studied. RESULTS: Routine histology revealed no significant histologic abnormality throughout the colon apart from four cases of melanosis coli. Ratio of the thickness of circular to longitudinal muscle was significantly lower in the left colon in constipated subjects. The myenteric plexus appeared morphologically normal in all subjects. S-100 protein, which stains neuronal supporting tissues, demonstrated an increase in the proportion of neural tissue in the myenteric plexus. There was an increased number of PGP-9.5 immunoreactive nerve fibers in the muscularis propria in constipated patients, and this was significantly higher in the ascending and descending colon. CONCLUSION: Intractably constipated patients have alterations in the neural composition of the colonic myenteric plexus and innervation of the circular muscle.Supported by a grant from Yonsei University Research Foundation, Seoul, Korea. Dr. Talbot is supported in part by the Imperial Cancer Research Fund.     

Distribution of nitric oxide synthase in stomach myenteric plexus of rats

AIM:To study the distribution of nitdc oxide synthese(NOS)in rat stomach myenteric plexus.METHODS:The distribution of NOS in gastric wall wasstudied in quantity and location by the NADPH-diaphorase(NDP)histochemical staining method and whole mountpreperation technique.RESULTS:NOS was distributed in whole stomach wall,mostof them were located In myenteric plexus,and distributed insubmucosal plexus.The shape of NOS positive neuronswas baslcally similar,most of them being round and oval inshape.But their density,size and staining intensity variedgreatly in the different parts of stomach.The density was 62±38 cells/mm~2(antrum),43±32 cells/mm~2(body),and 32±28 cells/mm~2(fundus),respectively.The size andstaining intensity of NOS positive neurons in the funduswere basically the same,the neurons being large and darkstained,while they were obviously different in antrum.Inthe body of the stomach,the NOS positive neurons were inan Intermediate state from fundus to antrum.There weresome beedlike structures which were strung together byNOS positiva varicosities in nerve fibers,some were closelyadherent to the outer walls of blood vessels.CONCLUSION:Nitric oxide might he involved in themodulation of motility,secretion and blood circulation ofthe stomach,and the significant difference of NOS positiveneurons in different parts of stomach myenteric plexus maybe related to the physiologic function of stomach.     

Effect of nitroblue tetrazolium on NO synthase and motor function of opossum esophagus

Nitric oxide mediates neuromuscular events in the opossum esophagus. The NADPH diaphorase stain is used to localize nitric oxide synthase-containing enteric neurons. Cells stain by the NADPH diaphorase technique because they reduce nitroblue tetrazolium to the visible formazan. The effects of nitroblue tetrazolium on neuromuscular function and nitric oxide synthase of esophageal muscle were studied. The NADPH diaphorase stain was performed. Nitroblue tetrazolium inhibited lower esophageal sphincter relaxation, abolished the latency gradient of the off response, and inhibited nitric oxide synthase. The NADPH diaphorase technique stained myenteric plexus nerve cell bodies and nerve processes. Nitroblue tetrazolium is not a nonspecific muscle or nerve toxin, as nerve-mediated cholinergic responses, responses to exogenous nitric oxide, and responses to myogenic stimulation were maintained after nitroblue tetrazolium abolished the off response and lower esophageal sphincter relaxation. Nitroblue tetrazolium inhibits nitric oxide-mediated events and nitric oxide synthase. It stains neurons in the esophageal myenteric plexus.This work was supported by a Merit Grant and a Research Career Development Award from the Department of Veterans Affairs, and NIH grant DK 11242.     

Slow transit chronic constipation (Arbuthnot Lane's disease)

Seven patients (6 women, 1 man) with severe idiopathic chronic constipation, who underwent surgery with subtotal colectomy and ileorectal anastomosis, were investigated for the occurrence and density of nerve fibres, immunoreactive to different neuropeptides in the mucosa, submucosa, ganglia and smooth muscle in fresh specimens from the colon ascendens, the colon transversum and the colon descendens-sigmoideum. The following substances were studied: enkephalin, substance P, somatostatin, neuropeptide Y, vasoactive intestinal polypeptide, calcitonin gene-related peptide, bombesin, motilin, tyrosine hydroxylase, dynorphin and galanin. Nerve fibres immunoreactive to CGRP occurred in large numbers in the myenteric ganglia of the patients with severe idiopathic chronic constipation, whereas in the myenteric ganglia of the control cases they only occurred in low numbers. In two patients there was no detectable motilin immunoreactivity and in one patient only sparse in the mucosa and the smooth muscle. The other neuropeptides investigated occurred in the density and distribution previously reported in the normal gut. With the present technique there were indications that patients with severe idiopathic chronic constipation have a significant difference in the occurrence of immunoreactive nerve fibres to CGRP and motilin compared to control patients.     

Cellular and molecular basis of chronic constipation: Taking the functional/idiopathic label out

In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called "functional" or "idiopathic" disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of "functional" gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors’ work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.     

Nitric Oxide Synthase (NOS) Expression in the Myenteric Plexus of Streptozotocin-Diabetic Rats

Nitric oxide (NO) is an important inhibitoryneurotransmitter in the gut. Alterations in NO mediatedresponses have been described in diabetic animals. Thepresence of nitric oxide synthase (NOS) reflects the potential for NO synthesis and is found inneurons in the myenteric plexus. The aim of this studywas to determine changes in nitric oxide synthase (NOS)expression in the myenteric plexus of thegastrointestinal tract of diabetic rats at three months ofstreptozotocin-induced diabetes, compared to age matchedcontrols, using immunohistochemistry. Diabetic animalsshowed a decrease in NOS expression in the antrum, with 59.1 ± 7.3% of neurons beingpositive for NOS in diabetes compared to 81.2 ±4.7% in controls (P < 0.05). NOS expression induodenum, ileum, and colon of diabetic animals was notstatistically different from controls. Decreased expression of NOS inantrum may contribute to altered gastric emptyingobserved in diabetics.     

Chronic idiopathic intestinal pseudo-obstruction caused by a degenerative disorder of the myenteric plexus: the use of Smith's method to define the neuropathology

In this paper we report the pathologic basis of chronic idiopathic intestinal pseudo-obstruction in a patient who had a subtotal colectomy and ileorectal anastomosis for severe obstipation. Conventional light microscopy of the resected intestine showed an increased thickness of the longitudinal muscle, minimal amounts of smooth muscle fibrosis, and normal smooth muscle cells. The morphology of the myenteric plexus was difficult to interpret with this technique, but quantification of colonic neurons revealed a significantly decreased number compared with controls. Silver stains of the myenteric plexus by Smith's method showed: (a) patchy loss of nerve tracts with replacement by Schwann cells, (b) degeneration and decreased numbers of both argryophilic and argyrophobic neurons, (c) fragmentation and dropout of many axons, and (d) increased thickness and disorganized spatial arrangement of other axons. The pathology of this intestinal neuropathy could be missed by conventional light microscopy and may be apparent only when a silver technique is used to visualize the myenteric plexus.     

Jejunal diverticulosis with perforation as a complication of Fabry's disease

This study presents the case of a patient who had jejunal diverticulosis with perforation and abscess formation as a complication of Fabry's disease. Light microscopy disclosed glycolipid deposition in the neurons and nerve fibers of the intestinal nerve plexuses and smooth muscle. Silver stains of the myenteric plexus in the involved segment of the bowel showed enlarged, granular argyrophobic neurons and a marked decrease in the number of argyrophilic neurons, with those remaining being enlarged and distorted by the cytoplasmic glycolipid accumulation. These abnormalities of the myenteric plexus suggest that jejunal diverticulosis may be the result of a variety of disorders of the smooth muscle or myenteric plexus, or both. We propose that jejunal diverticulosis in our patient was a consequence of uncoordinated smooth muscle activity resulting from Fabry's involvement of myenteric plexus neurons, with mucosal protrusion through the smooth muscle.     

Colocalization of NADPH-diaphorase staining and VIP immunoreactivity in neurons in opossum internal anal sphincter

Nitric oxide and vasoactive intestinal polypeptide (VIP) are important inhibitory neurotransmitters mediating relaxation of the internal anal sphincter. The location and coexistence of these two neurotransmitters in the internal anal sphincter has not been examined. We performed a double-labeling study to examine the coexistence of nitric oxide synthase and VIP in the oppossum internal anal sphincter using the NADPH-diaphorase technique which is a histochemical stain for nitric oxide synthase. In perfusion-fixed, frozen-sectioned tissue, VIP-immunoreactive neurons were labeled using immunofluorescence histochemistry. After photographing the VIP-immunoreactive neurons, nitric oxide synthase was labeled using the NADPH-diaphorase technique. Ganglia containing neuronal cell bodies were present in the myenteric plexus for the entire extent of the internal anal sphincter. VIP-immunoreactive and NADPH-diaphorase-positive neurons were present in ganglia in the myenteric as well as the submucosal plexuses. Most of the VIP-immunoreactive neurons were also NADPH-diaphorase positive. VIP and nitric oxide synthase are present and frequently coexist in neurons in the internal anal sphincter of the opossum. These neurons may be an important source of inhibitory innervation mediating the rectoanal reflex-induced relaxation of the sphincter. The demonstration of the coexistence of these two neurotransmitters will be of fundamental importance in unraveling their relationship and interaction in the internal anal sphincter as well as other systems.Supported by DK-02094 (RBL) and DK-35385 (SR) from the National Institutes of Health and an institutional grant from Thomas Jefferson University.     

Reaggregation of Rat Dissociated Myenteric Plexus in Extracellular Matrix Gels

The aim of this study was to investigate the growth behavior of freshly dissociated myenteric plexus in a three-dimensional extracellular matrix (ECM) environment with and without stimulation of glial cell line-derived neurotrophic factor (GDNF). Therefore, cell suspensions of the dissected myenteric plexus of newborn rats were cultured in freshly prepared gels of commercially available mixtures of collagen, laminin, and hepatoglycans as a first step towards mimicking the natural environment of the myenteric plexus. The cultures were kept either in chemically defined serum-free medium alone or supplemented with GDNF. Cultures on polylysine-coated glass cover slips served as controls. Dissociated myenteric plexus grown on polylysine formed dense clusters of neurons with radially outgrowing nerve fibers, while the neurons cultured in the gel reaggregated to much smaller clusters. These contained, depending on the culture conditions, 2–10 neurons. The morphology of the network that was seen in the gels after a few days in vitro resembled very closely the in situ situation of the submucous plexus and the myenteric plexus in hypoganglionic children. Electron microscope investigations showed a high degree of organization with fiber bundles and vesicle-containing varicosities and growth cones. Independent of the method of culturing, GDNF obviously influenced the growth behavior of the dissociated plexus. The size of the ganglia was larger, and the secondary network denser when GDNF was supplemented. Moreover, the enteric neurons in the gel cultures tended to be larger in size when treated with GDNF. Three-dimensional cultures of dissociated myenteric plexus in an ECM gel might be a valuable tool towards the understanding of the formation of the enteric nervous system during development, especially considering pathological conditions such as Hirschsprungs disease or other dysganglionic diseases.     

Expression of the P2X2 receptor in different classes of ileum myenteric neurons in the female obese ob/ob mouse

AIM:To examine whether the ob/ob mouse model of obesity is accompanied by enteric nervous system ab-normalities such as altered motility METHODS:The study examined the distribution of the P2X 2 receptor (P2X 2 R) in myenteric neurons of female ob/ob mice. Specifically, we used immunohistochemistry to analyze the co-expression of the P2X 2 R with neuronal nitric oxide synthase (nNOS), choline acetyltrans-ferase (ChAT), and calretinin (CalR) in neurons of the small intestine myenteric plexus in ob/ob and control female mice In these sections, we used scanning confocal microscopy to analyze the co-localization of these markers as well as the neuronal density (cm 2 ) and area profile (μm2) of P2X 2 R-positive neurons In addition, enteric neurons were labeled using the nicotinamide adenine dinucleotide (NA H) diaphorase method and analyzed with light microscopy as an alternate means by which to analyze neuronal density and areaRESULTS:In the present study, we observed a 29 6% increase in the body weight of the ob/ob animals (OG) compared to the control group (CG) In addition, the average small intestine area was increased by approxi-mately 29 6% in the OG compared to the CG Immu-noreactivity (IR) for the P2X 2 R, nNOS, ChAT and CalR was detectable in the myenteric plexus, as well as in the smooth muscle, in both groups This IR appeared to be mainly cytoplasmic and was also associated with the cell membrane of the myenteric plexus neurons, where it outlined the neuronal cell bodies and their processes P2X 2 R-IR was observed to co-localize 100% with that for nNOS, ChAT and CalR in neurons of both groups In the ob/ob group, however, we observed that the neuronal density (neuron/cm 2 ) of P2X 2 R-IR cells was in-creased by 62% compared to CG, while that of NOS-IR and ChAT-IR neurons was reduced by 49% and 57%, respectively, compared to control mice The neuronal density of CalR-IR neurons was not different between the groups Morphometric studies further demonstrated that the cell body profile area (μm2) of nNOS-IR, ChAT-IR and CalR-IR neurons was increased by 34%, 20% and 55%, respectively, in the OG compared to controls Staining for NA H diaphorase activity is widely used to detect alterations in the enteric nervous system; however, our qualitative examination of NA H-diaphorase positive neurons in the myenteric ganglia revealed an overall similarity between the two groups CONCLUSION:We demonstrate increases in P2X2R expression and alterations in nNOS, ChAT and CalR IR in ileal myenteric neurons of female ob/ob mice compared to wild-type controls.     

Distribution and Colocalization of Nitric Oxide Synthase and Calretinin in Myenteric Neurons of Developing, Aging, and Crohn's Disease Human Small Intestine

The pattern of distribution and colocalizationof nitric oxide synthase and the calcium-binding proteincalretinin in myenteric neurons and nerve fibers wereexamined in the human small intestine from preterm fetuses (14-17 weeks of gestation), normaladults (mean age 50 years old), old age (mean age 80years old), and Crohn's disease patients (mean age 30years old) using NADPH-diaphorase histochemistry and immunohistochemical techniques. In all agegroups investigated, NADPH-diaphorase-reactive andcalretinin-immunoreactive neurons and nerve fibers wereseen throughout the myenteric plexus. The highestproportion of NADPH-diaphorase-reactive neurons was foundin the myenteric ganglia of old age intestines (56% ofprotein gene product-immunoreactive neurons) followed byfetal intestines (41%) and Crohn's intestine (30%) compared with intestines of controladults (20%). A similar trend was observed forcalretinin-immunoreactive neurons where the highestproportion of immunoreactive neurons was found in themyenteric ganglia of old age intestines (28% of proteingene product-immunoreactive neurons), followed by fetalintestines (22%), and Crohn's intestines (18%) comparedwith intestines of control adults (9%). A colocalization of NADPH-diaphorase activity and calretininimmunoreactivity was only seen in the myenteric neuronsof fetal intestines (2% of NADPH-diaphorase-reactiveneurons were also calretinin-immunoreactive). The pattern of distribution of NADPH-reactive andcalretinin-immunoreactive neurons in the myentericganglia of fetal intestine differs from that of theother age groups. In the fetal intestine, the myenteric neurons containing either calretinin orNADPH-diaphorase are distributed through out themyenteric ganglia with no specific orientation to oneanother. In the intestines of control adult, Crohn's,and old age patients, single largecalretinin-immunoreactive neurons are surrounded by anumber of small NADPH-diaphorase-positive neurons, withthis feature being more prominent in intestines ofold-age and Crohn's disease patients. In summary, a high number ofboth NADPH-diaphorase-reactive andcalretinin-immunoreactive neurons were seen in themyenteric ganglia of fetal, old age, and Crohn'sintestines; we discuss that there may be a role for nitric oxide andcalretinin in the process of development, aging, andpathological changes in the human intestine associatedwith alteration in the calcium homeostasis in the myenteric neurons.     

Evaluation of myenteric ganglion cells and interstitial cells of Cajal in patients with chronic idiopathic constipation

BACKGROUND AND AIMS: The aim of this study was to identify myenteric ganglion cells (MGC) and interstitial cells of Cajal (ICC) from the total colectomy specimen in patients with chronic idiopathic constipation. PATIENTS AND METHODS: Fourteen patients who had severe, intractable, long-standing (mean: 14 years) constipation underwent subtotal colectomy and ileorectal anastomosis. All resected specimens were investigated with hematoxylin and eosin (H&E) and immunohistochemical staining with anti-neurofilament monoclonal antibody NF(2)F(11) for MGC, and c-kit antibody for ICC. The numbers of MGC and ICC were counted for ascending (AC), descending (DC), and sigmoid colon (SC). We compared these data with those from ten control specimens. RESULTS: The number of MGC was significantly smaller in AC and DC of the constipated group than in the control group. Interestingly, SC contained a similar number of MGC. The two staining methods were equally effective for identifying MGC. The total ICC number in the constipated group was markedly lower in every segment. Most anatomical layers of the colon, including the submucosal border, circular muscle, and longitudinal muscle, revealed a similar tendency. However, in the myenteric plexus area there was no significant difference between the two groups. CONCLUSION: A quantitative decrease in MGC and ICC appears to be implicated in chronic idiopathic constipation.     

Comparison between idiopathic achalasia and achalasia caused by Chagas' disease: a review on the publications about the subject

BACKGROUND: Although idiopathic achalasia and achalasia caused by Chagas' disease have the same clinical manifestations and treatment, both with destruction of the esophageal myenteric plexus, it is possible that there are differences in the alterations of esophageal motility between the two diseases, caused by different grades of impairment of the excitatory and inhibitory esophageal neurons. AIMS: We performed a review of papers with results about the pathophysiology and esophageal motility alterations in idiopathic achalasia and Chagas' disease. DATE SOURCES: We reviewed papers which included data about the characteristics of idiopathic achalasia and Chagas' disease. DATA SYNTHESIS: Impairment of inhibitory esophageal neurons was shown in the two diseases. The results of the studies of the effects of atropine, edrophonium and botulin toxin suggested that the excitatory innervation is more intensely impaired in Chagas' disease than in idiopathic achalasia, explaining the increase in the lower esophageal sphincter pressure found in achalasia. The patients with Chagas' disease have more circulating muscarinic cholinergic receptor M2 autoantibodies than patient with idiopathic achalasia. The duration of the contractions in the esophageal body is longer in idiophatic achalasia than in Chagas' disease. CONCLUSIONS: The papers that studied Chagas' disease and idiopathic achalasia, mainly those which studied both diseases with the same methods, suggested that there are different grades of esophageal involvement by the two diseases, mainly the most important involvement of excitatory innervation in Chagas' disease than in idiopathic achalasia.     

Etiology and pathogenesis of achalasia: the current understanding

Idiopathic achalasia is an inflammatory disease of unknown etiology characterized by esophageal aperistalsis and failure of LES relaxation due to loss of inhibitory nitrinergic neurons in the esophageal myenteric plexus. Proposed causes of achalasia include gastroesophageal junction obstruction, neuronal degeneration, viral infection, genetic inheritance, and autoimmune disease. Current evidence suggests that the initial insult to the esophagus, perhaps a viral infection or some other environmental factor, results in myenteric plexus inflammation. The inflammation then leads to an autoimmune response in a susceptible population who may be genetically predisposed. Subsequently, chronic inflammation leads to destruction of the inhibitory myenteric ganglion cells resulting in the clinical syndrome of idiopathic achalasia. Further studies are needed to better understand the etiology and pathogenesis of achalasia-such an understanding will be important in developing safe, effective, and possibly curative therapy for achalasia.