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Background and aims: Determination of intracellular signalling pathways that mediate intestinal epithelial proliferation is fundamental to the understanding of the integrity and function of the intestinal tract under normal and [...]

Background and aims: Substance P (SP) release from sensory nerves induces neurogenic inflammation. Neutral endopeptidase (NEP) degrades SP, thereby limiting its proinflammatory effects. Intestinal inflammation following Trichinella spiralis infection markedly [...]

Our current knowledge of motor and sensory functions in the human gut is critically reviewed, showing how the two may interact to produce symptoms in patients with functional gastrointestinal disorders. [...]

Crohn's disease is an inflammatory bowel condition affecting the ileum (the lower portion of the small intestine), characterized by abdominal pain, anemia, loss of weight, and other gastrointestinal complaints. One cellular abnormality manifested by Crohn's disease patients is a defect in the ability of neutrophils (a type of white blood cell involved in the body's natural defense system) to destroy foreign substances. In normal individuals, a characteristic burst in metabolic rate is seen during activation of neutrophils; this corresponds to the increased energy requirement of the neutrophils while they kill invading microorganisms, and reflects activation by the neutrophils of an enzyme system (NADPH oxidase system) necessary for their action. To determine whether activation of this pathway is defective in patients with Crohn's disease, 15 healthy volunteers and 25 patients with Crohn's disease were studied. Three different chemical stimuli were used to activate neutrophil NADPH oxidase (as determined by production of superoxide anions, a metabolic product of this pathway). Neutrophils isolated from healthy patients produced significantly more superoxide anion in response to two of the three stimuli than did neutrophils from Crohn's disease patients. The suppression was seen in all patients with Crohn's disease, but the degree of suppression was independent of the severity of the disease (making it unlikely that neutrophil dysfunction is a secondary effect of the disease). Hence, NADPH oxidase activation is impaired in neutrophils from patients with Crohn's disease. Whether or not this defect can be linked to the intestinal symptoms seen in these patients remains to be determined. (Consumer Summary produced by Reliance Medical Information, Inc.)

Celiac disease is a condition in which nutrients are not absorbed properly from the jejunum (a segment of the small intestine), resulting in malnutrition, diarrhea, bleeding, and low blood levels of calcium. Patients suffering from celiac disease are allergic to wheat-derived proteins (such as gliadin) and produce a class of blood-borne antibodies (immunoglobulin A; IgA) that is directed against the wheat proteins. Estimation of blood IgA levels is now routinely used to screen for celiac disease. Little is known about the nature of the immune response of the gastrointestinal mucosa (the inner lining of the gastrointestinal tract), which might operate independently of, or in concert with, the humoral (blood) immune response. A study was done to investigate this, and to determine whether indices of mucosal immune system function that can be obtained by relatively non-invasive means (e.g. antibody concentrations in saliva) are good predictors of jejunal immune responses. Blood, saliva, and fluid aspirated from the jejunum of 26 patients with untreated celiac disease, 22 patients with treated celiac disease, and 28 normal subjects were analyzed for immunoglobulin levels. In addition, intestinal secretions were collected from similar numbers of patients drawn from those three populations. Antibody levels in jejunal aspirate were elevated in patients with untreated celiac disease; this was partially normalized by dietary treatment, but some antibody levels remained high even with successful treatment. Untreated patients had higher levels of anti-gliadin antibodies than either treated patients or normal controls for all body fluids tested. There was a positive correlation between antibody levels in jejunal aspirate and in fluid aspirated from the stomach; however, there was no correlation between saliva antibody levels and those in jejunal aspirate. This indicates that salivary antibodies do not reflect the intestinal immune response. (Consumer Summary produced by Reliance Medical Information, Inc.)

Irritable bowel syndrome is a poorly defined group of symptoms relating to defecation, the nature of which is controversial, and for which there is no diagnostic test. Commonly reported symptoms include erratic bowel habits, diarrhea, constipation, and abdominal pain. There is disagreement among physicians as to the degree to which irritable bowel syndrome reflects normal patient concern with abnormal gastrointestinal function rather than excessive preoccupation with normal day-to-day variation in defecation. To objectively quantify the characteristics of irritable bowel syndrome, three groups of patients were studied. The subjects were 26 female patients being treated on an outpatient basis for irritable bowel syndrome, 27 women who admitted to symptoms of irritable bowel syndrome but who had not consulted a doctor (noncomplainers), and 27 healthy control subjects. All women monitored their bowel habits, stool consistency, subjective evaluation of gastrointestinal function, and physical symptoms for 30 days. All groups of subjects reported instances of pain and bloating, but this occurred much more frequently in the patient group. Defecation was much more erratic (both in timing and stool consistency) in the patient group, and there was also a distortion of the normal relationship between stool consistency and subjective report of bowel function, perhaps reflecting rectal irritation in these patients. Straining to finish defecating, followed by feelings of incomplete emptying of the bowels, was nine times more prevalent among irritable bowel patients. Noncomplainers fell between the patients and normal controls on almost all of the parameters measured, but were closer to the controls than to the patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Duodenal ulcer is a condition in which the inner lining of the duodenum (the first portion of the small intestine) becomes inflamed, causing bleeding and pain; if untreated, the wall of the duodenum may perforate, a potentially fatal occurrence. Duodenal ulcer is caused by gastric acid eating through the mucosal barrier protecting the inner lining of the duodenum. Over 95 percent of duodenal ulcer sufferers are infected with the bacteria Helicobacter pylori (H. pylori). Many, if not all, H. pylori-infected individuals have high blood levels of the gastrointestinal hormone gastrin (which causes secretion of gastric acid); these elevated levels are immediately decreased when the infection has been treated. Metabolic byproducts (ammonium) emanating from the H. pylori may be responsible for the increased gastrin levels. To evaluate this, eight patients who had a duodenal ulcer in the past year and tested positive for H. pylori infection were given intragastric infusions of urea (which is broken down by the bacteria into ammonium). While this procedure caused a 15-fold increase in ammonium levels, it had no effect on blood gastrin. One month after eradication of the H. pylori infection, the same test was run. There was a similar increase in ammonium levels, and a similar failure to increase blood gastrin. These results indicate that bacteria-generated increases in intragastric ammonium levels do not raise blood gastrin levels by an appreciable amount. (Consumer Summary produced by Reliance Medical Information, Inc.)

Crohn's disease is a gastrointestinal disorder in which part of the gastrointestinal tract, usually the ileum (a segment of the small intestine), becomes inflamed. The cause of Crohn's disease is not understood, but it has been postulated that an impaired response to certain forms of bacterial infection may be one causal factor. Neutrophils are a type of white blood cell that form one of the body's defenses against invading microorganisms. Candida albicans is a common bacterium which is present in the gastrointestinal tract of between 14 and 47 percent of the normal population. When unchecked, C. albicans can cause a variety of inflammatory diseases, possibly including Crohn's disease. To investigate whether there is an impairment of neutrophil function in Crohn's disease patients, the ability of neutrophils isolated from normal subjects and those with Crohn's disease to kill C. albicans was determined. After 30 and 60 minutes of incubation with C. albicans, neutrophils from Crohn's disease patients had killed significantly less C. albicans than neutrophils from normal patients. There was no evidence for inhibitory factors from other blood components, and there was no evidence for impairment of the mechanism of phagocytosis (ingestion and digestion of the bacteria by the neutrophil). A cellular defect in the neutrophil is most likely responsible for the diminution in candidacidal activity (ability to kill C. albicans) of these neutrophils. (Consumer Summary produced by Reliance Medical Information, Inc.)

Chronic intractable constipation is a disease afflicting predominantly young women, in which spontaneous bowel movements occur only once or twice per month. In some women, there is a deformation of the pelvis that results in a mechanical impediment to the passage of feces through the large intestine. In others, there is no apparent cause for the disorder, and these women are generally resistant to conventional medical treatment. Surgical treatment, removal of part of the colon, is usually the only resort, and it is not always successful. In order to investigate the neuromuscular basis of this disorder, eight women with chronic intractable constipation and 12 normal controls were studied. Mechanical sensors were placed in the colon, rectum, and anus of each subject, and intestinal neuromuscular activity was automatically recorded with a portable encoder box and cassette recorder. A distinctive pattern of pressure changes (known as sampling responses) was seen in the normal controls and consistent with previously reported data. These sampling responses occurred at a greatly reduced frequency in the constipated subjects. In addition, rectal motor complexes (wavelike contractions of the rectum necessary for normal defecation) were greatly reduced in amplitude in the constipated subjects. These results suggest that reduced transit of feces from the colon to the rectum may be part of the underlying cause of the constipation, and that a motor neuropathy (defective nerve supply to the large intestine) may be responsible. (Consumer Summary produced by Reliance Medical Information, Inc.)

Crohn's disease, or regional ileitis, is an inflammatory condition of the intestine characterized by diarrhea, abdominal pain, anemia, weight loss, and symptoms of intestinal obstruction. The cause of Crohn's disease is not known, but it has been suggested that hypersensitivity to dietary antigens (substances which mobilize a response by the immune system) may be an important factor. It has been reported that in Crohn's disease patients (but not in patients with the similar inflammatory condition ulcerative colitis), blood levels of antibodies against a strain of baker's yeast (Saccharomyces cerevisiae) are increased. To determine whether this increased antibody level would generalize to other strains of yeast commonly used in industrial applications, a study was carried out with 15 Crohn's disease patients, 15 ulcerative colitis patients, and 15 healthy controls. Levels of antibodies to 11 of the 12 strains of yeast tested were increased in the Crohn's disease patients, but not in either the ulcerative colitis or control group. The antibody response to the 11 strains was not homogeneous, suggesting that the various strains have different effects on activation of the immune system, and that the increased antibody levels are not simply the result of increased intestinal permeability to antigens. Levels of antibodies to the infective yeast microorganism Candida albicans did not differ between the patients and control subjects. (Consumer Summary produced by Reliance Medical Information, Inc.)

Hypersensitivity in functional gastrointestinal disorders Patients with functional gastrointestinal disorders present with abdominal symptoms which have no apparent organic cause. It has been well established that these patients have a [...]