Muscarinic receptor regulation of the esophagus and lower esophageal sphincter.
Explore the source record for details and available documents.
Cholinergic Antagonists↗
Biomedical subjects
B Greenwood
Publications and source records attributed to B Greenwood.
Regional content of enteric substance P and vasoactive intestinal peptide during intestinal inflammation in the parasitized ferret.
Our aim was to characterize and quantitate changes in two key neuropeptides, substance P (SP) and vasoactive intestinal peptide (VIP), that are involved in governing neurally-mediated gastrointestinal (GI) reflex activity during enteric inflammation in the ferret. Neuropeptide content was determined by radioimmunoassay of extracts of jejunal, ileal and colonic muscularis externa from uninfected ferrets and ferrets infected with enteric stages of the parasitic nematode, Trichinella spiralis. Increased myeloperoxidase activity (MPO), an enzymatic marker of inflammation, occurred in all three gut regions. Histopathological changes were present only in the small intestine. Significant reductions were detected in both SP (72% decrease) and VIP (62% decrease) in the inflamed jejunum. Ileal concentrations of both SP (77% decrease) and VIP (46% decrease) were also decreased during T. spiralis infection compared to uninfected ferrets. Only SP (58% decrease) concentration showed a significant change in colonic tissues from infected ferrets; colonic VIP was unaltered. Parasite-induced inflammation caused significant changes in peptide-containing enteric neural pathways and might contribute to functional GI motor disturbances that occur during nematode infections in mammalian hosts.
Animals↗
An improved microassay for Plasmodium falciparum cytoadherence using stable transformants of Chinese hamster ovary cells expressing CD36 or intercellular adhesion molecule-1.
Stable transformants of Chinese hamster ovary (CHO) cell lines expressing high levels of human CD36 or intercellular adhesion molecule-1 (ICAM-1) have been produced as target cells for cytoadherence of Plasmodium falciparum-infected erythrocytes. An improved adherence microassay has been designed using small sample volumes and allowing convenient and reliable measurements on a large number of samples. The assay can be used both with purified proteins spotted on plastic and with the stably transformed CHO cell lines. The same assay plate can be evaluated either microscopically or by scintillation counting after use of 3H-hypoxanthine-labeled parasites. Using the microassay, functional expression of the transfected receptor molecules on CHO-CD36 and CHO-ICAM was confirmed using parasites with different cytoadherence phenotypes and cytoadherence inhibition experiments with a panel of anti-CD36 antibodies. The use of isolates from The Gambia confirmed the applicability of these assays for laboratory studies of these isolates.
Amino Acid Sequence↗
Effect of mebeverine hydrochloride on jejunal motility and epithelial transport in the anesthetized ferret.
Previous in vitro and in vivo studies demonstrate that mebeverine, administered to isolated smooth muscle preparations or given intravenously, (i.v.), acts as an antispasmodic agent and may be useful in treating intestinal hypermotility. Whether mebeverine affects intestinal mucosal transport is, however, unknown. The aim of the present study was to characterize the effect of mebeverine on both small intestinal motor activity and electrogenic epithelial transport in the urethane anesthetized ferret. The effects of mebeverine were compared following i.v. and intrajejunal (i.j.) administration. Following both routes of drug administration mebeverine dose dependently inhibited jejunal motility, with the i.j. route being more potent. However, when administered i.v. but not i.j., the doses of mebeverine that inhibited jejunal motility also significantly reduced heart rate and arterial blood pressure. Mebeverine (0.1-10 mg/kg) administered i.v. had no significant effect on epithelial transport as measured by a change in transmural potential difference. However, when dosed i.j., mebeverine (0.1-10 mg/kg) induced a decrease in potential difference towards lower lumen negativity, which was suggestive of a decrease in fluid secretion or enhancement of absorption. In conclusion, the results confirm in vivo the antispasmodic effect of mebeverine and suggested that mebeverine can influence epithelial transport, probably in the direction of enhanced intestinal absorption.
Anesthesia↗
Mucin and protein release in the rabbit jejunum: effects of bethanechol and vagal nerve stimulation.
The role of the vagus nerve and cholinergic mechanisms in the control of rabbit jejunal mucin and protein release was investigated in vivo. In anesthetized animals, a 10-cm segment of the jejunum was cannulated and perfused with saline. Perfusate was collected and analyzed for mucin (by immunoassay) and protein. Bilateral cervical vagotomy had no effect on basal mucin or protein output, suggesting that the vagus nerve does not exert a tonic control on jejunal macromolecule secretion. Electrical stimulation of the vagi did not alter mucin release, even in the presence of muscarinic cholinergic (scopolamine) or adrenergic (propranolol and phentolamine) blockade. In contrast, protein output increased significantly after vagal stimulation, an effect inhibited by scopolamine. In both vagotomized and vagally intact rabbits, the cholinergic agonist bethanechol (200 micrograms/kg intraperitoneally) induced a scopolamine-sensitive increase in both mucin and protein output. Predominantly serum proteins were released into intestinal perfusates after vagal or cholinergic stimulation. It is concluded that the extrinsic vagus nerve does not regulate rabbit jejunal mucin secretion in vivo and that cholinergic control of intestinal goblet cells is implemented entirely by the intrinsic enteric nervous system. In addition, cholinergic or vagal stimulation increases intestinal vascular and epithelial permeability, resulting in the passage of serum proteins into the lumen, possibly by opening tight junctions and paracellular pathways.
Animals↗
Epidemiology of acute lower respiratory tract infections, especially those due to Haemophilus influenzae type b, in The Gambia, west Africa.
Mortality surveys undertaken in rural areas of The Gambia, a small country on the west coast of Africa, indicate that acute lower respiratory tract infections (ALRI) are the most frequent cause of death among children and that approximately 1 in 25 rural Gambian children dies from an ALRI before the age of 5 years. Community surveys suggest that each child experiences an average of one episode of ALRI accompanied by radiographic changes before reaching this age. Etiologic studies have shown that pneumococci, Haemophilus influenzae type b (Hib), and respiratory syncytial virus are the most important causes of ALRI in Gambian children who present to a hospital, and the same three organisms are probably the major causes of severe ALRI in rural communities. Hib probably accounts for 5%-10% of cases of severe ALRI in Gambian children, and because the incidence of severe ALRI is high, an effective Hib conjugate vaccine might save as many childhood deaths by preventing pneumonia as by preventing meningitis.
Child↗
Prostaglandins and modulation of small bowel myoelectric activity.
We explored the effects of prostaglandins (PG) F2 alpha and E2 on the motor and myoelectric activity of the small intestine using closed intra-arterial injections in conscious chronically instrumented dogs. PGF2 alpha (0.125-5 micrograms) and PGE2 (1-10 micrograms) were injected via a T tube into a branch of the superior mesenteric artery perfusing a 15-cm segment of jejunum. Experiments were performed on four dogs in which the recording devices had been implanted above, below, and within the perfused segment. PGF2 alpha given during phase I of the migrating myoelectric complex cycle induced phasic contractions in the perfused segment of intestine in a dose-dependent manner. Atropine (50-100 micrograms), hexamethonium (15 mg), or TTX (10-15 micrograms) administered before the injection of PGF2 alpha failed to inhibit the effects of PGF2 alpha. In contrast pretreatment of the perfused segment with verapamil (2.5 mg) or PGE2 (1-5 micrograms) abolished the effects of PGF2 alpha. Moreover, PGE2 injected 5 min after the administration of PGF2 alpha inhibited the PGF2 alpha-induced contractions. Administration of PGE2 alone (3-10 micrograms) before the arrival of phase III activity in the perfused segment abolished phase III from this segment of intestine. Our studies indicate opposing effects of PGF2 alpha and PGE2 on small intestinal myoelectric and contractile activities. PGF2 alpha has a direct excitatory effect on the intestinal smooth muscle, which is calcium channel dependent but independent of intrinsic nerves. PGE2 has an inhibitory effect both on the spontaneous and PGF2 alpha-induced small intestinal myoelectric and contractile activity.
Animals↗
Nicotine stimulates esophageal peristaltic contractions in cats by a central mechanism.
The aim of the present study was to 1) characterize nicotine-induced peristalsis in the feline esophagus and 2) determine the site of action of nicotine. Experiments were done on ketamine-sedated cats. Esophageal contractions were measured using a multilumen catheter assembly system. After recording 1 degree and 2 degrees peristaltic sequences nicotine (50-100 micrograms/kg iv) was administered. Nicotine induced a peristaltic contraction through the esophageal striated and smooth muscle part of the esophagus, which was not associated with any mylohyoid electromyogram activity or pharyngeal response, although the upper esophageal sphincter did relax. Addition of either atropine (20-50 micrograms/kg iv) or hexamethonium (10-20 mg/kg iv), a peripherally acting nicotinic antagonist, did not affect the striated muscle portion of the nicotine-induced esophageal contractile response but antagonized the smooth muscle response. However, mecamylamine (0.5-1 mg/kg iv), a ganglionic antagonist that crosses the blood-brain barrier, abolished the esophageal response to nicotine. Succinylcholine (0.5-1 mg/kg iv) abolished the striated muscle response without affecting the nicotine-induced smooth muscle contractility. Finally, the nicotine-induced peristaltic sequence was abolished after bilateral cervical vagotomy. In conclusion, nicotine, administered peripherally, activates central brain stem mechanisms that mediate a peristaltic sequence through the feline esophagus.
Animals↗
DNA fingerprinting in the epidemiology of African serogroup A Neisseria meningitidis.
The restriction endonuclease (RE) technique was used to compare 172 meningococcal group A strains collected between 1969 and 1990, mainly from countries of the so-called African Meningitis Belt, the Gambia and Ethiopia. The 64 strains from various African countries (Niger, Chad, Burkina Faso, Cameroon, Morocco, Djibouti) were distributed within 3 main restriction enzyme patterns (REPs); the 77 Gambian strains fell into 5 REPs and the 24 Ethiopian strains into 2 such patterns. Several of the main REPs were formed by clusters of closely related clones. Clones, very similar to dominating REPs of the 1960s in Niger, Burkina Faso and Cameroon, were in the 1980s found to be strongly represented in the Gambia to the extreme west of the Meningitis Belt. One of the Gambian clones from 1983-86 was identical to an Indian clone recovered in New Delhi 1986-87. Another clone was detected in 1983 in the Gambia, in 1989 again in the Gambia as well as in Ethiopia, and in 1990 in Tanzania. Our results are largely in line with those of previous studies based on modern techniques of protein and isoenzyme electrophoresis. The RE method is useful mainly for the exact genotypic differentiation of closely related clones, and seems to be a valuable complement to phenotypic tools for epidemiological mapping of Group A meningococcal infection.
Africa↗
Antibody response to pneumococcal capsular polysaccharide vaccine in African children.
Antibody titers to six pneumococcal polysaccharides were measured by enzyme-linked immunosorbent assay in Gambian children before and 1 month after vaccination with a 23-valent pneumococcal capsular polysaccharide vaccine at the ages of 2, 4, 6 or 9 months or at 5 to 10 years of age. IgG responses to type 1, 3 and 5 polysaccharides were seen in children in all age groups. Responses to type 19F and 23F polysaccharides were seen only in the oldest children. Few children of any age responded to immunization with type 6A pneumococcal polysaccharide. The immune response of Gambian infants to immunization with six components of a polyvalent pneumococcal polysaccharide vaccine was comparable with that described previously in Finnish infants and would be unlikely to provide substantial protection against invasive pneumococcal disease.
Antibodies, Bacterial↗
Medullary sites mediating some abdominal vagal reflexes in the ferret using [14C]2-deoxyglucose.
The central projections of some abdominal visceral afferents passing through the vagal communicating branch were studied in anesthetized ferrets using [14C]2-deoxyglucose autoradiography. The reflex effects of electrical stimulation of the vagal communicating branch were studied while measurements of jejunal motor activity and transmural potential difference, a marker of electrogenic epithelial transport were made concurrently. The aim of this study was to examine brainstem projections of some afferent fibers in the communicating branch of the thoracic vagus nerve that are necessary for the reflex regulation of small intestinal motor activity and epithelial transport. In urethane-anesthetized ferrets, electrical stimulation of the cut central end of the vagal communicating branch increased jejunal motor activity and electrogenic epithelial transport. In addition, glucose utilization in the left medial sub-nucleus of the nucleus tractus solitarius and the dorsal motor nucleus of the vagus was significantly increased as compared with sham-operated non-stimulated control animals. Identical areas on the contralateral side of the brain showed no change in glucose utilization as compared with sham-operated non-stimulated controls. This functional brain-mapping study strongly suggests that the left medial sub-nucleus of the nucleus tractus solitarius and the dorsal motor nucleus of the vagus, in the ferret, are involved in processing alimentary afferent activity from both the small intestinal musculature and epithelium as well as the reflex changes in efferent vagal nerve activity to the same regions of the alimentary tract.
Afferent Pathways↗
The demonstration of HLA-D proteins by an amplified alkaline phosphatase/anti-alkaline phosphatase detection system in wax-processed human lung tissue fixed in 10% formol saline.
Explore the source record for details and available documents.
Alkaline Phosphatase↗
Effects of substance P and vasoactive intestinal polypeptide on contractile activity and epithelial transport in the ferret jejunum.
Previous studies in the ferret demonstrated that vagal nerve stimulation induced an atropine-resistant water secretion. Substance P and vasoactive intestinal polypeptide are possible mediators of this secretory response. The objectives of this study were to investigate the in vivo effects of substance P and vasoactive intestinal polypeptide on the jejunal musculature and epithelium. Substance P caused an increase in jejunal motility, water secretion, and transmural potential difference. Cholinergic blockade did not affect the substance P-induced contractions, but did reduce the increase in transmural potential difference, suggesting an inhibition of water secretion. Vasoactive intestinal polypeptide abolished motor activity; however, it induced an increase in transmural potential difference that was atropine and tetrodotoxin resistant. By immunohistochemical methods, immunoreactive vasoactive intestinal polypeptide and immunoreactive substance P were localized to both nerve cell bodies and nerve fibers in the ferret intestine. Determination of intestinal concentrations of vasoactive intestinal polypeptide and substance P in the ferret showed concentrations of these two neuropeptides that were similar to those in human intestine and demonstrated much higher concentrations of these substances in the muscular layer than in the epithelial layer. Our data demonstrate that in the ferret substance P excites and vasoactive intestinal polypeptide inhibits jejunal motor activity. However, both peptides increase water secretion. Our results suggest that in response to vagal stimulation, neuronally released substance P or vasoactive intestinal polypeptide may participate in the atropine-resistant water secretion.
Action Potentials↗
Measuring cellular immune responses to malaria antigens in endemic populations: epidemiological, parasitological and physiological factors which influence in vitro assays.
Measurements of in vitro cellular immune responses to malaria antigens are influenced by a variety of external factors. The physiological status of the donor, which is affected by, for example, malaria infection, intercurrent illness and pregnancy, can influence the lymphoproliferative response to specific antigens. Prior exposure to malaria antigens, determined by malaria endemicity, seasonal variations in transmission and the degree of polymorphism of the particular antigen, will also affect the prevalence and intensity of responses. Malaria-related immunosuppression may be both generalised and antigen specific. Although in vitro responses to malaria antigens are profoundly suppressed in acutely infected individuals, there is evidence that lymphocyte activation does occur in vivo. We conclude that longitudinal studies, correlating specific immune responses with subsequent malaria morbidity are required, to identify potentially protective antigens and appropriate effector mechanisms.
Acute Disease↗
Submucosal plexus alone integrates motor activity and epithelial transport in rat jejunum.
It has been well established in several mammalian species, including humans, that contractions of jejunal smooth muscle correlate temporally with increases in mucosal ion transport. Furthermore, this correlation is abolished through local application of neurotoxins, suggesting interaction of enteric neurons. The purpose of this study was to determine whether the myenteric plexus is involved in this correlation. In the rat jejunum in vivo, we simultaneously measured phasic changes in intraluminal pressure and transmural potential difference (PD) as indicators of smooth muscle motor activity and epithelial ion transport, respectively. We compared the temporal association of these parameters in control animals with animals in which either the extrinsic nerves only or the extrinsic nerves and the myenteric plexus of a 5-cm jejunal segment had been ablated 30 days previously. A one-to-one coupling between muscle contractions and transmural PD fluctuations was observed in all animals; ablation of the extrinsic and/or myenteric neurons did not eliminate this correlation. We conclude that, in the rat jejunum, the submucosal plexus alone can integrate the reflex that couples ion secretion to muscle contraction.
Animals↗
The immunocytochemical preservation of IgE and mast cells of the rat.
The localisation of IgE to mast cells of rats infested with Nippostrongylus brasiliensis has been studied in an attempt to find a fixation procedure which will best preserve (a) the antigenicity of IgE for immunocytochemical demonstration, and (b) the histochemical staining properties of mast cells. A fixative comprising Carnoy's fluid and picric acid (CPA) best fulfilled these criteria, allowing localisation of IgE to both the plasma membrane and cytoplasm of mucosal mast cells of rat small intestine, but only to the plasma membrane of connective tissue mast cells of rat tongue. Formaldehyde-containing fixatives prevented labelling of IgE in the cytoplasm of mucosal mast cells.
Animals↗
Mast cells in conjunctiva affected by cicatricial pemphigoid.
Ocular cicatricial pemphigoid (OCP) is characterized by progressive conjunctival subepithelial fibrosis often leading ultimately to corneal blindness. Mast cells have been shown to play a role in several fibrotic disorders, but the role of mast cells in OCP is unknown. The authors compared the mast cell population in conjunctival biopsy specimens from 14 OCP patients and from six controls by using specific histochemical stains for mast cell subsets. The total mast cell number and the ratio of connective tissue mast cells to mucosal mast cells (MMCs) were significantly higher in OCP than in normal conjunctiva (P less than 0.05). This report is the first analysis of mast cell subsets in human ocular tissue. The results suggest that connective tissue mast cells (CTMCs) may play an important role in OCP and that therapy directed toward mast cells and their mediators may be an appropriate avenue for further exploration.
Adult↗
Cholinergic control of smooth muscle peristalsis in the cat esophagus.
The aim of this study was to examine in detail the effects of selective cholinergic and other pharmacological antagonists on primary and secondary peristalsis in the smooth muscle of the cat esophagus in order to fully characterize the cholinergic contribution to peristalsis in this species. Primary and secondary peristalsis in the smooth muscle part of the feline esophagus was completely abolished by atropine, 4-dephenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (a selective M2 muscarinic antagonist), hexamethonium, and high doses of nicotine. Pirenzepine (a selective M1 muscarinic antagonist), propranolol, and phentolamine were without effect, as were naloxone, methysergide, and pyrilamine. From these findings we conclude that primary and secondary peristalsis in feline esophageal smooth muscle involves nicotinic ganglionic neurotransmission as well as postganglionic release of acetylcholine that acts directly on muscarinic receptors located on the smooth muscle. Peristalsis in esophageal striated muscle does not involve either synaptic transmission or muscarinic receptors.
Animals↗