Migration of the myoelectric complex after interruption of the myenteric plexus: intestinal transection and regeneration of enteric nerves in the guinea pig

The effects of surgical interruption of the myenteric plexus (myectomy), extrinsic denervation of a length of small intestine, or transection and reanastomosis of the intestinal wall on migration of phase III of the migrating myoelectric complex was studied in guinea pigs. In addition, the recovery of phase III migration and the regrowth of intestinal nerves and muscle across the reanastomosis was studied at various times up to 60 days after surgery. At 6-9 days after surgery, phase III did not migrate past the myectomy during 50%-60% of recorded migrating myoelectric complexes and transection and reanastomosis of the intestinal wall blocked aboral progression of phase III in 90% of cases. Extrinsic denervation did not alter phase III migration through the denervated segment. Phase III migration past the reanastomosis recovered with time after surgery; 80% recovery occurred by 60 days after surgery. Immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin were used as markers for intestinal nerves that were cut by transaction. Immunoreactivities for vasoactive intestinal peptide and gastrin-releasing peptide are contained in myenteric neurons that project in an oral to anal direction to other myenteric ganglia and to the circular muscle. Immunoreactivity for somatostatin is contained in nerve fibers projecting aborally to other myenteric ganglia. At 7-15 days after surgery, there were accumulations of immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin in nerve fibers on the oral side of the reanastomosis, but nerve fibers containing these peptides were not observed in myenteric ganglia or circular muscle close to the anal edge. At 23-28 days, immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin nerve fibers were traced across the reanastomosis and nerve terminals were detected in ganglia and muscle close to the lesion on the anal side. Nerve fibers traversed the lesion in all cases at 57-60 days and vasoactive intestinal peptide-, gastrin-releasing peptide-, and somatostatin-immunoreactive nerve terminals were detected in the first two to three rows of myenteric ganglia on the anal side. Regrowth of intestinal muscle followed a similar time-course to that observed for nerves. These data suggest that interruption of the myenteric plexus alone does not completely block phase III migration. In addition, recovery of phase III migration past a reanastomosis is associated with a restoration of both nervous and mechanical connections.     

Peptide-containing neurons in different regions of the submucous plexus of human sigmoid colon.

Specimens of the sigmoid colon were obtained from male and female patients (n = 11) with carcinoma of the colon or rectum and studied immunohistochemically for vasoactive intestinal polypeptide-, somatostatin-, substance P-, neuropeptide Y-, calcitonin gene-related peptide-, met- and leu-enkephalin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-containing nerves. In the subdivisions of the submucous plexus (namely, Schabadasch's, Meissner's, and the intermediate plexuses), substance P- and vasoactive intestinal polypeptide-immunoreactive nerve fibers were the most numerous, and equal densities of these nerves were found in all three layers. In contrast, few neuropeptide Y-, met-enkephalin-, leu-enkephalin-, calcitonin gene-related peptide-, somatostatin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-immunoreactive nerves were found in these regions. The nerve cell bodies of the submucous plexus contained vasoactive intestinal polypeptide, substance P, leu-enkephalin, somatostatin, and 5-hydroxytryptamine but not neuropeptide Y, met-enkephalin, calcitonin gene-related peptide, and dopamine beta-hydroxylase. Vasoactive intestinal polypeptide-containing nerve cell bodies were found in all three subdivisions. Substance P-, leu-enkephalin-, and somatostatin-immunoreactive nerve cell bodies were found in Schabadasch's plexus and the intermediate region of the submucous plexus, but they were absent from Meissner's plexus; 5-hydroxytryptamine-containing nerve cell bodies were only observed in Schabadasch's plexus. The possible function of the neuropeptide-, dopamine beta-hydroxylase-, and 5-hydroxytryptamine-containing neurons in the different layers of the submucous plexus is discussed.     

Changes in adrenergic and peptidergic nerves in the submucous plexus of streptozocin-diabetic rat ileum.

The effect of streptozocin diabetes on the distribution of adrenergic and peptidergic nerves in the submucous plexus of rat ileum was investigated and compared with the changes in the myenteric plexus of the same region of ileum. There was an increase in the intensity of immunoreactivity in vasoactive intestinal polypeptide- and neuropeptide Y-like immunoreactive nerve fibers and neurons and a decrease in calcitonin gene-related peptide-like immunoreactivity but no change in substance P- and dopamine beta-hydroxylase-like immunoreactivity in the nerve fibers and neurons of the submucous plexus of both 8- and 16-wk streptozocin-diabetic rat ileum. However, in the myenteric plexus of the diabetic rat ileum, there was enlargement of varicosities and an increase followed by a slight decrease in the intensity of immunoreactivity of vasoactive intestinal polypeptide- and dopamine beta-hydroxylase-like immunoreactive nerve fibers and neurons, increased substance P-like immunoreactivity in diabetes at 16 wk, and an initial decrease (at 8 wk) followed by a recovery of calcitonin gene-related peptide-like immunoreactivity at 16 wk, but no change in neuropeptide Y-like immunoreactivity. The markedly different changes in peptidergic and adrenergic nerves between the two enteric plexuses show that diabetic neuropathy induced by streptozocin is not selective and involves factors other than neurotransmitter types.     

Distributions of neuropeptides in the human esophagus

The distributions of nerve cells and fibers with immunoreactivity for the peptides substance P, somatostatin, enkephalin, vasoactive intestinal peptide, gastrin-releasing peptide, and neuropeptide Y and the enzyme tyrosine hydroxylase were examined in 25 samples of human esophagus. These were compared with samples of stomach and intestine. In the smooth muscle of the muscularis externa, the muscularis mucosae, and beneath the epithelium, the most abundant nerve fibers contained vasoactive intestinal peptide and neuropeptide Y, in contrast to the scarcity of substance P, enkephalin, somatostatin, and gastrin-releasing peptide. Gastric and intestinal samples contained dense populations of fibers containing vasoactive intestinal peptide, neuropeptide Y, substance P, and enkephalin in the equivalent layers, but somatostatin- and gastrin-releasing peptide-immunoreactive fibers were scarce. Complete coexistence of vasoactive intestinal peptide and neuropeptide Y in nerve fibers within the muscle layers was demonstrated in the esophagus, but not in gastric and intestinal samples. The myenteric plexus along the length of the esophagus contained cell bodies and fibers reactive for vasoactive intestinal peptide, neuropeptide Y, enkephalin, and substance P. Somatostatin-immunoreactive cell bodies were very rare in the myenteric plexus, no gastrin-releasing peptide-immunoreactive cell bodies were seen, and both somatostatin and gastrin-releasing peptide-immunoreactive fibers were rare. In the upper esophagus, striated muscle bundles did not contain nerve fibers reactive for these peptides but immunoreactive fibers were seen in the muscularis mucosae and subepithelium. It is concluded that the esophagus has a different pattern of innervation by peptide-containing neurons than the stomach and intestines. Esophageal neurons can be classified into separate classes on the basis of their peptide content.     

Substance P-containing nerves in the human small intestine. Distribution, ultrastructure, and characterization of the immunoreactive peptide

Light and electron microscopic immunocytochemical techniques were used to examine the distribution and ultrastructure of substance P-immunoreactive nerves in human jejunum and distal ileum. The organization of human enteric substance P-containing nerves closely resembled that in other species. Dense arrays of varicose immunofluorescent fibers occurred in myenteric and submucous ganglia (which contained immunoreactive nerve cell bodies) and in the mucosa. There were fibers in both muscle layers, in the muscularis mucosae, and around blood vessels. Fibers in the myenteric plexus contributed to both ascending and descending pathways. Substance P-immunoreactive axon profiles contained small round and large round vesicles and were apposed to nerve cell bodies, and nonimmunoreactive and immunoreactive axon profiles. Synapselike contacts were occasionally observed on nerve cell bodies and processes. The substance P-like material was characterized by high pressure liquid chromatography and radioimmunoassay and found to be indistinguishable from the authentic undecapeptide. These results suggest that enteric nerves containing substance P may play similar roles in humans as in other species.     

Electron microscopic study of neuropeptide Y-containing nerve elements of the guinea pig small intestine

Neuropeptide Y-containing nerve cell bodies and processes were identified by electron microscopic immunocytochemistry in the guinea pig small intestine. Labeled nerve processes were numerous in the myenteric plexus. However, a few immunoreactive nerve fibers were found in all layers of the small intestine. Some of the immunoreactive nerve processes were found in close apposition to the epithelial cells of the crypts of Lieberkühn and to endothelial and smooth muscle cells. The neuropeptide Y-containing nerve cell bodies were preferentially located in the submucous ganglia. In the myenteric plexus many synaptic connections were observed between the neuropeptide Y-immunoreactive nerve fibers and unlabeled nerve cell bodies and other nerve fibers. These findings provide a morphologic basis for the possibility that neuropeptide Y may act as a transmitter and exert postsynaptic effects on intrinsic neurons, in addition to participating in the regulation of smooth muscle activity and epithelial cell functions.     

Localization of endothelinlike immunoreactivity and endothelin binding sites in human colon

The potent vasoconstrictor endothelin was originally isolated from vascular endothelial cells but has since been found in several other tissues. The aim of this study was to establish whether endothelinlike immunoreactivity occurs in human enteric nerves and to identify endothelin binding sites using immunocytochemical and in vitro autoradiographic techniques. Endothelinlike immunoreactivity was localized to nerve bundles throughout the colon and to most of the ganglion cells of the two major plexuses, many of which costored vasoactive intestinal polypeptide. High-affinity (dissociation constant = 0.35 +/- 0.014 nmol/L; mean +/- SEM) binding sites for endothelin 1, with an apparent binding capacity of 92 +/- 6.3 amol/mm2 (mean +/- SEM), were demonstrated in the myenteric plexus, with less dense binding being found in the submucous plexus, mucosa, muscle layers, and blood vessel walls. Competition data suggested two populations of binding sites, both showing high affinities for endothelins 1 and 2, vasoactive intestinal constrictor, and sarafatoxin b but differentiated by their affinity for endothelin 3 and sarafatoxin c. This study provides evidence that endothelin is a neuropeptide in the human intestine with binding sites on neural plexuses and mucosa, suggesting a role in the modulation of intestinal motility and secretion.     

Serotoninergic neurons in human fetal intestine: an immunohistochemical study

The distribution of 5-hydroxytryptamine-like immunoreactivity was studied in whole-mount preparations of intestine from human fetuses. Immunoreactive nerve cell bodies were located in the myenteric plexus and were occasionally found in the submucous plexus; they were often seen to have long processes. Varicose fibers were found in the ganglia and internodal strands of the myenteric and submucous plexuses, in the deep muscular plexus of the circular muscle, and in the walls of some small mesenteric blood vessels immediately outside the intestine. This study provides evidence for the presence of serotoninergic nerves in the human intestine.     

Peptide-containing nerve fibers in the stomach wall of rat and mouse

Peptide-containing nerve fibers were found to be numerous in the glandular stomach of the rat and mouse. The immunoreactive neuropeptides demonstrated included vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), gastrin-releasing peptide (GRP), substance P (SP), enkephalin, somatostatin, cholecystokinin, and neuropeptide Y (NPY). The density and distribution of the various peptide-containing fibers did not differ overtly between the pyloric and oxyntic gland areas except for the GRP fibers, which were fewer in the pyloric than in the oxyntic mucosa. The entire VIP nerve fiber population was found to also contain PHI. Immunoreactive NPY was found to occur in the VIP/PHI fibers (VIP/PHI/NPY fibers) in the smooth muscle and intramural ganglia of both rat and mouse and in the mucosa of the mouse. Mucosal VIP/PHI fibers in the rat did not contain any NPY-like material. Perivascular NPY fibers in both species and mucosal NPY fibers in the rat did not contain VIP or PHI. The mucosa harbored numerous GRP fibers and VIP/PHI (rat) or VIP/PHI/NPY (mouse) fibers, and a modest number of NPY (rat) and SP fibers. In the submucosa the peptide-containing nerve fibers were found mainly in the ganglia and around blood vessels. Blood vessels received a rich supply of NPY fibers; the number of perivascular VIP/PHI, GRP, and SP fibers was much lower by comparison. The smooth muscle and myenteric ganglia harbored not only VIP/PHI/NPY, GRP, and SP fibers but also enkephalin, somatostatin, and cholecystokinin fibers. Gastrin-releasing peptide, VIP/PHI/NPY, SP, and enkephalin nerve cell bodies occurred in the myenteric ganglia. As studied in the rat, vagal denervation did not affect the density and distribution of the various peptide-containing nerve fibers. After sympathectomy, mucosal and perivascular NPY fibers disappeared. The other types of peptide-containing nerve fibers were not affected.     

Abnormalities of peptide-containing nerve fibers in infantile hypertrophic pyloric stenosis

The distributions of nerve cells and fibers with immunoreactivity for the peptides enkephalin, gastrin-releasing peptide, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal peptide were examined in specimens of myenteric plexus and external muscle from the pylorus of 20 infants with hypertrophic pyloric stenosis. These were compared with peptide distributions in pyloric samples from unaffected infants and adults. In the normal pylorus the circular muscle was richly supplied with fibers reactive for enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide. In pyloric stenosis, these immunoreactive fiber bundles were either missing or less than 5% of normal. In contrast, there were reactive cell bodies and nerve fibers in the myenteric plexuses of both normal and affected specimens. In the samples from cases of stenosis, swollen nerve fibers that appeared to be in the process of degeneration were frequently encountered. It is concluded that infantile hypertrophic pyloric stenosis is associated with a loss of peptide immunoreactivity in nerve fibers in the circular muscle, although the same peptides are still revealed in fibers and in nerve cell bodies in the myenteric plexus.     

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.     

Distribution and coexistence of peptides in nerve fibers of the external muscle of the human gastrointestinal tract

The nerve fibers that supply the external muscle of the human gastrointestinal tract were examined for their immunoreactivity to the neuropeptides enkephalin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal peptide, for tyrosine hydroxylase (a catecholamine-synthesizing enzyme), and for coexistence between immunoreactivities in nerve fibers. Studies on coexistence revealed that the majority of reactive nerve fibers could be placed in one of two classes: (a) those fibers with reactivity to enkephalin or substance P, or both, and (b) fibers containing one or both of the peptides neuropeptide Y and vasoactive intestinal peptide. Many fibers immunoreactive for vasoactive intestinal peptide or neuropeptide Y, or both, were found throughout the external smooth muscle of the gastrointestinal tract, but neuropeptide Y-reactive fibers were less common in the small and large intestines than in the stomach and esophagus. Fibers immunoreactive for enkephalin or substance P, or both, were sparse in the esophagus, increased in numbers to reach maximal frequency in the pylorus, and maintained a similar frequency in the small and large intestines. Fibers with somatostatin or tyrosine hydroxylase immunoreactivity were rare. In general, sphincter regions were similar to nonsphincter regions in peptide-immunoreactive fiber numbers and types, except that the internal anal sphincter had no enkephalin-immunoreactive fibers and very few substance P-reactive fibers. Moderate numbers of fibers reactive for neuropeptide Y and vasoactive intestinal peptide were found in the internal anal sphincter. It is suggested that enkephalin and substance P are in excitatory fibers and that vasoactive intestinal peptide and neuropeptide Y are in fibers inhibitory to the external muscle.     

Peptidergic innervation of the human esophageal smooth muscle

Studies were performed to define the peptidergic nature of intramural nerves in the human esophagus. Cryosections of uninvolved surgically resected tissues from 14 individuals were studied by immunofluorescence for the localization of 10 neuropeptides. Myenteric neurons showed bombesin-, calcitonin gene-related peptide-, galanin-, substance P-, vasoactive intestinal polypeptide-, leucine-enkephalin-, methionine-enkephalin-, neuropeptide Y-, and somatostatin-like immunoreactivity. Submucous neurons had all the above except neuropeptide Y, methionine-enkephalin, leucine-enkephalin, and bombesin. Both groups of neurons received nerve terminations positive for calcitonin gene-related peptide, galanin, neuropeptide Y, substance P, and vasoactive intestinal polypeptide. Myenteric neurons additionally received terminations positive for neuropeptide Y, methionine-enkephalin, and somatostatin. All muscle layers had varicose fibers that reacted for calcitonin gene-related peptide, galanin, neuropeptide Y, and substance P. Longitudinal and circular muscle received few nerves reactive for leucine-enkephalin, whereas methionine-enkephalin was localized in a few nerve endings in the circular muscle. Somatostatin- and bombesin-reactive nerves occurred in longitudinal muscle. No cholecystokinin-reactive nerves were found. This study extends the results of previous studies and shows the previously undescribed presence of calcitonin gene-related peptide- and galanin-reactive nerves in the human esophagus and identifies neuropeptides that may serve as motor, sensory, and modulatory neurotransmitters of esophageal nerves.     

Distribution of nitric oxide synthase-containing nerves in the aganglionic intestine of mutant rats: A histochemical study

We examined the distribution of nerves containing nitric oxide synthase in the intestine of congenitally aganglionic rats, using a reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemical method for whole-mount and cryostat specimens. A constricted intestinal segment extends from the terminal ileum to the anus in this mutant. No nerve elements with the activity were found in the affected terminal ileum, cecum, and proximal colon. Although intrinsic ganglionic neurons were absent along the constricted intestine, nerve fibers with the activity were found in both the submucous and intermuscular layers distal to the proximal colon. These fibers increased in density towards the rectum, forming hypertrophic nerve bundles and unusual fiber networks. However, positive fibers were never seen within the circular and longitudinal musculature of the constricted lesion. Some of these hypertrophic nerve bundles were continuous with ectopic ganglia that were situated in the adventitial connective tissue around the lower rectum and in the submucosa near the anus. The hypertrophic nerve bundles seemed to have an extrinsic origin; some of them may have originated from ectopic ganglia. These results suggest that the defective distribution of nerves containing nitric oxide synthase may be involved in the pathogenesis of congenital colonic aganglionosis.     

An in vitro study of the projections of enteric vasoactive intestinal polypeptide-immunoreactive neurons in the human colon

The anatomical basis of the peptidergic neural control of the human colon is largely unknown. In this study, in vitro retrograde tracing methods have been used on fresh human colon to determine the projection pathways of the enteric nerves and, in particular, those containing vasoactive intestinal polypeptide, one of the most abundant and potent of the gut neuropeptides. Two components of the submucous plexus were identified, the inner one projecting to the lamina propria, and the outer to the circular muscle. The lengths of projections within the submucous plexus were up to 5-14 mm in all directions. Myenteric ganglion cells projected to both longitudinal and circular muscles, for distances of up to only 5 mm. The subpopulation of nerves containing vasoactive intestinal polypeptide arose mainly from the submucous plexus and projected up to 6.5 mm anally, 5 mm orally, and 14 mm within the submucous layer to the mucosa or circular muscle. These findings provide entirely new data on the neuroanatomy of the human colon and may help in the understanding of the neural control of colonic secretion and motility.     

糖尿病大鼠胃窦部CGRP,VIP神经免疫组织化学及图像分析

为了解糖尿病时胃肠道肽能神经的改变，应用免疫组织化学及图像分析法对糖尿病大鼠胃窦部ＣＧＲＰ、ＶＩＰ神经进行了观察和分析。     

Distribution and origin of the peripheral innervation of rat cervical esophagus

Several neurotransmitters, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), galanin, enkephalin, calcitonin-gene related peptide (GGRP), substance P, as well as nitric oxide synthase (NOS), and the noradrenergic marker tyrosine-hydroxylase (TH) were localized by immunocytochemistry in the cervical esophagus of rat. Nerve fibers containing the neuropeptides, NOS, and TH were distributed in the myenteric plexus, around muscle bundles and small blood vessels. Injection of the retrograde tracer True Blue (TB) into the cervical esophagus resulted in the appearance of labeled nerve cell bodies in the superior cervical, the stellate, the nodose, the sphenopalatine, the dorsal root ganglia at levels C₂–C₇, and in local ganglia close to the thyroid. Most of the TB-labeled nerve cell bodies in the superior cervical ganglia contained NPY. In the stellate ganglion, a few labeled nerve cell bodies contained VIP whereas an additional few cell bodies stored NPY. In local ganglia, the majority of labeled cell bodies contained VIP. In the nodose ganglion and cervical dorsal root ganglia, the majority of the labeled nerve cell bodies stored CGRP. The results indicate that the cervical esophagus has a dense innervation with multiple neurotransmitters emanating from several ganglia. As judged by the pattern of nerve fiber distribution, they may regulate esophageal peristalsis and blood flow, some of them possibly in a cooperative manner.     

Noradrenergic and peptidergic innervation of the extrinsic vessels and microcirculation of the rat cremaster muscle

The noradrenergic and peptidergic innervation of the extrinsic vessels and microcirculation of the rat cremaster muscle was examined. Catecholamine-containing nerves were identified histochemically by glyoxylic acid-induced fluorescence and tyrosine hydroxylase immunoreactivity (TH-IR). The extrinsic pudic-epigastric artery and vein as well as the entire intramuscular arteriolar network was innervated by noradrenergic axons. The capillaries and intramuscular venules of the cremaster muscle were devoid of a noradrenergic innervation. Immunohistochemical double-labeling demonstrated that most, if not all, of the TH-IR axons also possessed neuropeptide Y immunoreactivity (NPY-IR), implying colocalization of the norepinephrine and NPY in the perivascular nerves. No vasoactive intestinal peptide immunoreactivity (VIP-IR) was found, except for occasional VIP-IR axons associated with the pudic-epigastric artery. Substance P immunoreactive (SP-IR) axons formed a sparse plexus around the arteries and larger arterioles. Calcitonin gene-related peptide immunoreactivity (CGRP-IR) had a similar distribution to the SP-IR axons. CGRP-IR was also observed in axons alongside some smaller arterioles and capillaries. The extrinsic vessels and intramuscular arteriolar network of the rat cremaster muscle are innervated by noradrenergic axons which contain NPY and by presumed sensory nerves containing SP and/or CGRP. Both types of nerves may contribute to regulation of microvascular function.     

Peptides in the gastrointestinal tract in human immunodeficiency virus infection. The GI/HIV Study Group of the University of Calgary.

The presence of immunoreactivity to the neuronal phosphoprotein B-50 and the peptides bombesin, calcitonin gene-related peptide, galanin, neurotensin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal polypeptide was examined in biopsy specimens from the duodenum and rectum of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative male homosexual patients. The distribution of B-50 and the peptides was correlated with HIV serology, number of CD4+ lymphocytes, and the presence of HIV in biopsy culture. There was a very low incidence of enteric pathogens in both groups of patients. It was found that HIV-seropositive patients had a greater incidence of abnormal patterns of immunoreactivity (reduced intensity and/or density of innervation) in enteric nerves and enteroendocrine cells than HIV-seronegative patients. A reduction of substance P immunoreactivity was significantly correlated with reduced CD4+ lymphocyte count and HIV status; a similar trend was also seen for somatostatin and vasoactive intestinal polypeptide. Using B-50 as a marker, it was found that both groups of patients had altered patterns of immunoreactivity in rectal nerves. The findings of this study suggest that some of the clinical symptoms associated with HIV infection may be caused by a specific HIV enteropathy that influences enteric nerve and/or enteroendocrine cell function by altering the density of peptide immunoreactivity.     

Intrinsic pancreatic nerves after mechanical denervation of the extrinsic pancreatic nerves in dogs.

Little is known about the influence of cutting the extrinsic pancreatic nerves on the morphology and function of the intrapancreatic nerves in dogs. For this reason, intrapancreatic nerves of mongrel dogs were studied, using electron microscopy and immunohistochemistry, after truncal vagotomy, after celiac and superior mesenteric ganglionectomy, and after a combination of both operations, i.e., removing all extrinsic nerves of the pancreas. Dogs with intact extrinsic and intrinsic pancreatic nerves served as controls. Studies were performed 1-2 weeks and up to 5 months after one or both denervation procedures. For immunohistochemical and electron microscopic studies the animals were perfused with glutaraldehyde-formaldehyde-picric acid solution and the tissue was embedded in Epon or paraffin. Both immunohistochemical and electron microscopic studies revealed that signs of degenerating intrapancreatic nerves occurred only in the early phase (up to 30 days) after operation. After 60 days, hypertrophy of pancreatic nerve fibers was observed. The most striking finding was that the integrity of the intrapancreatic ganglia and nerves was almost preserved after complete extrinsic denervation. In controls there was a strong intrapancreatic innervation with vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI), substance P (SP), and neuropeptide Y (NPY) nerves. SP and NPY-nerves significantly decreased after the different denervation procedures, but the other peptidergic nerves were not altered by truncal vagotomy, ganglionectomy, or the combination of both procedures. We conclude that the dog pancreas contains extensive intrinsic peptidergic nerves, which, with the exception of SP and NPY-nerves, are greatly independent of the integrity of the extrinsic nerves.