Acupuncture inhibits vagal gastric acid secretion stimulated by sham feeding in healthy subjects.

In a prospective randomised study, the effect of acupuncture on sham feeding stimulated gastric acid secretion was investigated. In eight healthy volunteers (five men, three women, mean (SEM) age 26.3 (4.7) years) various methods of acupuncture were performed. Apart from the sham procedure, the acupuncture was performed at the classic acupuncture points. Electroacupuncture reduced gastric acid secretion expressed as median (range) significantly during the first 30 minute period to 1.6 (0-5.2) mmol compared with 3.8 (2.3-14.5) mmol (p < 0.05) during control period (sham feeding without acupuncture). Inhibition of gastric acid secretion by electroacupuncture was also significant during the second 30 minute period (0.2 (0-5.6) v 3.6 (0.3-9.1) mmol; p < 0.05) and for peak acid output (0.8 (0.2-5.1) v 7.6 (3.4-12.1) mmol; p < 0.05). Transcutaneous electrical nerve stimulation also resulted in significant reduction of gastric acid secretion during the first 30 minute period (1.0 (0-3.6) mmol v 3.8 (2.3-14.5) mmol; p < 0.05), and peak acid output (3.6 (1.2-12.0) v 7.6 (3.4-12.1) mmol; p < 0.05). The classic needle acupuncture, laser acupuncture, and sham acupuncture had no significant effect on gastric acid secretion. This study shows firstly that in healthy volunteers, only the versions of acupuncture using more pronounced stimulation (electroacupuncture, transcutaneous electrical nerve stimulation), but not those with only mild stimulation of the nerves (classic needle acupuncture, laser acupuncture), and secondly only acupuncture performed at defined points lead to significant reduction in gastric acid secretion.

[Diagnostic guidelines in diarrhea]. / Diagnostischer Leitfaden bei Diarrhoe.

Acute diarrhea is usually short-lasting; therefore, diagnostic procedures are mainly concerning the degree of dehydration. With longer duration of high fever or bloody diarrhea, microbiologic stool tests are necessary. Proctosigmoidoscopy is indicated in case of dysenteric disease or suspected antibiotic-as-associated pseudomembranous colitis. In chronic diarrhea, the most important diagnostic procedure is a careful history. Side effects of drugs and food-related causes are especially noticeable, as are indices of an organic origin, e.g. unwanted weight loss or blood in the stools. Also, careful history and physical examination are essential for the decision about laboratory tests, tests of gastrointestinal function or endoscopy.

[Therapeutic guidelines in diarrhea]. / Therapeutischer Leitfaden bei Diarrhoe.

In acute diarrhea water and electrolyte losses are compensated for by oral or intravenous rehydration. Oral rehydration solutions contain primarily glucose or glucose polymers and sodium as well as other electrolytes. In acute and chronic diarrhea, loperamide is the most potent and safe antidiarrheal drug. Antibiotics are used without hesitation only in invasive diarrhea. In chronic diarrhea, diagnostic work up must precede therapy. Potentially diarrheogenic drugs or foods have to be eliminated. In most cases, when the diagnosis has been established, specific therapeutic measures are available.

[Geriatric diseases of the upper digestive tract]. / Geriatrische Erkrankungen des oberen Verdauungstraktes.

During aging, secretion and motility of the upper GI tract slow down. The reduction of these functions, however, does not create complaints. In the higher age groups, a number of symptoms from age-dependent diseases occur more frequently, e.g., dysphagia in response to cerebral ischemia, or disturbed gastric emptying caused by diabetic visceral neuropathy. Moreover, certain GI diseases occur more often in the elderly, e.g., chronic atrophic gastritis, NSAR-induced gastric ulcers, malignancies, and others. In contrast, almost nothing is known about diseases or symptoms of the GI tract that might be specific for the elderly. With only a few exceptions, there are no age-dependent clinical differences. Nevertheless, intestinal diseases often develop more rapidly and the mortality is higher in the elderly than in younger people.

[Meteorism]. / Meteorismus.

Gastrointestinal bloating is a common complaint met within the general practitioner's office. The most important cause of this symptom is an increase in the volume of gas in the gastrointestinal tract. Differential diagnoses include aerophagia, ingestion of gas-producing foods, gastric hypersecretion, bacterial overgrowth in the small intestine, disordered gastrointestinal transit, malabsorption or maldigestion of carbohydrates. In addition, nonulcer dyspepsia and the irritable bowel syndrome must be excluded. The diagnosis is based on a history of eructation, heart burn, flatulence and diarrhea, dietary habits, physical examination, laboratory analysis and apparative diagnostic measures. Therapy depends on the underlying cause of the disease.

[Nutrition and allergy]. / Ernährung und Allergie.

In many patients, commercial, industrially processed, but often also unprocessed ("natural"), food cause postprandial complaints. If skin or respiratory complaints occur in addition, it is safe to assume the presence of a food allergy. Often, however, it is not the foodstuff itself, but molds or mold enzymes added during processing that are responsible, and other additives may also act as allergens. Quite frequently, the condition is not strictly an allergy, but a pseudoallergy. This paper deals both with the diagnostic evaluation and treatment.

Fate and effects of the alpha-glucosidase inhibitor acarbose in humans. An intestinal slow-marker perfusion study.

The alpha-glucosidase inhibitor acarbose has been successfully used in diabetic patients to decrease the postprandial rise in blood glucose. The aim of the present experiments was to investigate the fate and effects of acarbose along the small intestine using a slow-marker perfusion technique. In 8 healthy volunteers, jejunal and ileal loads of acarbose, glucose, and total carbohydrates were determined following a liquid, 400-kcal formula meal containing either 200 mg of acarbose or placebo. Preprandial and postprandial plasma concentrations of glucose and several polypeptide hormones were determined. Recovery of acarbose during 4 h was 65% +/- 9% (mean +/- SEM) of ingested dose in the ileum but 94% +/- 9% in the jejunum, indicating that the compound was neither degraded nor absorbed by the intestine to a major degree. After acarbose administration, ileal loads of glucose and total carbohydrates were considerably higher, whereas postprandial plasma concentrations of glucose, insulin, and gastric inhibitory polypeptide were lower when compared with placebo. The retardation of carbohydrate digestion to be inferred from these findings is confirmed by significantly elevated plasma concentrations of enteroglucagon after acarbose administration compared with placebo administration.

Calmodulin-mediated effects of loperamide on chloride transport by brush border membrane vesicles from human ileum.

We investigated whether the synthetic opiate loperamide-HCl is able to regulate specific transport systems for sodium and chloride in brush border membrane vesicles (BBMVs) from human ileum and whether such activities are mediated by calcium/calmodulin. In BBMVs we studied Na+/H+ antiport, Cl+/OH- antiport, Na+/Cl- cotransport, and the Cl- conductive pathway. Brush border membrane vesicles were incubated with 10 microM loperamide over 4 h at 5 degrees C before the uptake experiments. In ileal BBMVs, loperamide stimulated intravesicular accumulation of Na+ in the presence of Cl- and vice versa. After 1 min of incubation, the stimulatory effect was 35% +/- 5% (p less than 0.005) of the control without loperamide. Loperamide also stimulated Cl-/OH- antiport by 30% +/- 5% (p less than 0.005) in BBMVs of ileum. In addition, we studied the role of Ca2+/calmodulin in the action of loperamide on chloride transport by human BBMVs. In loperamide-pretreated BBMVs, calmodulin activity was significantly decreased (12 +/- 2 vs. 38 +/- 4 pmol/mg protein). When loperamide-pretreated vesicles were incubated with 2 microM calcium (free concentration) plus 5 microM calmodulin for 1 h at 5 degrees C, complete inhibition of the stimulatory effect of loperamide on Cl-/OH- antiport and Na+/Cl- cotransport was observed. Increasing the Ca2+/calmodulin activity of loperamide-pretreated BBMVs with 2 microM calcium plus 5 microM calmodulin led to a significant inhibition of Cl-/OH- antiport and Na+/Cl- cotransport by 40% +/- 5% (p less than 0.005).

Effect of the somatostatin analogue SMS 201-995 on ATP-dependent calcium transport of basolateral vesicles from human duodenum.

Brush border membrane vesicles (BBMV) and basolateral membrane vesicles (BLMV) were simultaneously prepared from surgically resected pieces of morphologically intact human duodenum with a modified Percoll gradient centrifugation method. Alkaline phosphatase was enriched 20-fold in BBMV, whereas (Na+ + K+)-stimulated adenosine triphosphatase was enriched 15-fold in BLMV. BBMV and BLMV were preincubated with 3 microM synthetic somatostatin-14 or 3 microM SMS 201-995 for 10 min at 5 degrees C. In BBMV calcium, sodium, D-glucose, L-alanine, and D-mannitol uptake was unaffected by somatostatin-14 and SMS 201-995. In BLMV we found two Ca++ transport systems: Na+/Ca++ exchange and ATP-driven Ca++ transport. Somatostatin-14 had no effect on either of the two transport mechanisms. SMS 201-995 had no effect on Na+/Ca++ exchange but significantly inhibited basolateral ATP-dependent Ca++ transport (-40% +/- 5%, p less than 0.005).

Gastric mucosal cell loss caused by aspirin and alcohol.

Gastric epithelial cell loss was studied in healthy volunteers before and after intragastric instillation of four aspirin (ASA) formulations and three strengths of alcohol. Each test solution was administered three times over a period of three hours during one of the experiments. Three of the four aspirin formulations significantly increased gastric epithelial cell loss. Microencapsulated aspirin increased gastric epithelial cell loss significantly, but only after the third dose. Alcohol, 10% (wine), increased cell loss to a similar extent as did microencapsulated aspirin. Alcohol, 20% (campari), and 40% (whisky), significantly enhanced cell loss to such a degree as was elicited by the two strengths of soluble aspirin. Thus, gastric cell loss increased dose-dependently after both aspirin and alcohol. The data suggest that, in man, gastric epithelial cell damage caused by different aspirin formulations and alcohol concentrations is reproducible and dose-dependent.

Effect of two potent calmodulin antagonists on calcium transport of brush border and basolateral vesicles from human duodenum.

In the present in-vitro study we investigated the possible role of the calmodulin-antagonistic drugs loperamide and calmidazolium in the regulation of transepithelial Ca2+ transport of human duodenum. Brush border membrane vesicles and basolateral membrane vesicles were simultaneously prepared from surgically resected pieces of morphologically intact human duodenum with a modified Percoll-gradient centrifugation method. Brush border and basolateral membrane vesicles were characterized using enzyme marker analysis and electron microscopy: alkaline phosphatase was enriched 20-fold in brush border membrane vesicles, whereas [Na+ + K+]-stimulated adenosine triphosphatase was enriched 15-fold in basolateral membrane vesicles. Calmodulin activity was determined by a specific radioimmunoassay after solubilizing brush border and basolateral membrane vesicles in 1% Triton X-100. In basolateral membrane vesicles, we found no calmodulin activity. In brush border membrane vesicles calmodulin activity was impaired by 50% after pre-incubation with loperamide or calmidazolium. We measured calcium, sodium, D-glucose and D-mannitol uptake with a rapid filtration technique. Before the transport experiments, brush border and basolateral membrane vesicles were pre-incubated with 5 microM loperamide or 5 microM calmidazolium for 60 min at 5 degrees C. In drug-pretreated, brush border membrane vesicles calcium uptake was significantly reduced after 1 min incubation (-25% +/- 5%, P less than 0.05); this effect was completely reversed in the presence of 5 microM calmodulin. In basolateral membrane vesicles, we found two Ca2+ transport systems: (1) Na+/Ca2+ exchange and (2) ATP-dependent Ca2+ transport. In basolateral membrane vesicles loperamide had no effect. Calmidazolium had no effect on Na+/Ca2+ exchange, but significantly inhibited ATP-dependent Ca2+ transport. This effect could not be reversed by calmodulin.

Functional defect of zinc transport in patients with Crohn's disease.

In the present study, we investigated the question whether the zinc deficiency in Crohn's disease is, at least partly, related to defective zinc entry at the jejunal brush border membrane. Brush border membrane vesicles (BBMV) were prepared from surgically resected pieces of morphologically intact human jejunum by a Mg++ precipitation method. We studied zinc, D-glucose, sodium and D-mannitol uptake into BBMV in 27 patients: 1) 20 patients with Crohn's disease 2) 7 controls. In 8/20 patients with Crohn's disease we found a significant decrease in zinc uptake (-25% +/- 5%, p less than 0.05) into BBMV. This impairment of zinc uptake in 40% of our patients with Crohn's disease was not associated with changes in the transport rates for D-glucose, sodium or D-mannitol. In addition no differences in enzyme marker concentrations or electron microscopic appearance were found.

Review: loperamide--a potent antidiarrhoeal drug with actions along the alimentary tract.

The synthetic opioid, loperamide, reduces stool weight, frequency of bowel movements, urgency and faecal incontinence in acute and chronic diarrhoea. In man, the mechanism of action of loperamide is primarily the retardation of small-intestinal transit, and the stimulation of anal sphincter pressure and of faecal continence. This mechanism increases mucosal contact time, allowing more complete absorption of electrolytes and water. Studies in animals have demonstrated inhibitory effects of opiates and opioids, including loperamide, on fluid and electrolyte secretion induced by various secretagogues. By comparison, opiates have smaller if any antisecretory or pro-absorptive actions in man. The discrepancies between the results obtained in animal and human experiments are most certainly due to the large differences between drug doses used. Besides its opiate-receptor binding and stimulating activity, loperamide also behaves as a calcium-calmodulin antagonist and as a calcium channel blocker. These two other mechanisms might contribute to loperamide's antidiarrhoeal activity. Loperamide is more effective and safer than other opiates or opioid drugs in the treatment of both infantile and adult diarrhoea of various causes, although adequate fluid and electrolyte replacement remain the prime need.

[Reversible functional disorders of the intestinal tract caused by abdominal radiotherapy]. / Reversible Funktionsstörungen des Intestinaltraktes durch abdominelle Strahlentherapie.

In 20 patients with malignancies receiving abdominal radiotherapy, tests for disturbed intestinal functions were performed at the beginning and at the end of the therapy and after 6 to 12 month following radiation. Four noninvasive tests were performed: 75Se-homotaurocholate (75SeHCAT) test for estimation of bile acid malabsorption; Schillings test for quantification of vitamin B12 absorption; H2-breath analysis before and after a test meal containing lactose as a parameter of lactose malabsorption; and 51Cr-EDTA test for estimation of intestinal permeability. Both bile acid and vitamin B12 absorption decreased significantly towards the end of abdominal radiotherapy in more than 50% of patients. Only one patient developed lactose malabsorption. After 6 to 12 month, these abnormalities had completely disappeared. In contrast, small intestinal permeability did not increase during radiotherapy but was significantly elevated 6 to 12 month following treatment as the only indication of chronic injury of small intestinal mucosa. During radiotherapy, a significant correlation existed between the severity of diarrhea and the degree of bile acid malabsorption.

Effect of inhibitors on sodium and chloride transport in brush border vesicles from human jejunum and ileum.

Brush border vesicles were isolated from surgically resected pieces of human jejunum and ileum using a Mg2+/EGTA precipitation method. When compared to the homogenate, the final membrane preparation contained alkaline phosphatase at a 14 times higher concentration and almost no (Na++K+)-stimulated adenosine triphosphatase. An Na+/H+ antiport could be demonstrated in the jejunum by imposing a pH gradient between the interior and the outside of the vesicles (pHinside 5.2, pHoutside 7.2). In the presence of amiloride or harmaline, Na+/H+ antiport was inhibited by 60 +/- 5% (p less than 0.05) or 65 +/- 5% (p less than 0.05), respectively. In vesicles of human ileum we found an Na+/H+ antiport and in contrast to the jejunum a Cl-/OH- antiport could be demonstrated by imposing a pH gradient (pHinside 5.2, pHoutside 7.2). Besides this double-exchange mechanism for sodium and chloride, a Na+/Cl- cotransport and a Cl- conductive pathway could be detected in ileal brush border vesicles. In the presence of the anion transport inhibitors, furosemide, SITS and DIDS activities of Cl-/OH- antiport and Na+/Cl- cotransport were suppressed by 30 +/- 5% (p less than 0.05), 35 +/- 5% (p less than 0.05) and 40 +/- 5% (p less than 0.05), respectively. We conclude that absorption of sodium and chloride in the absence of organic solutes is mediated through different transport mechanisms at the luminal plasma membrane, which are in part subject to regulation by sodium and chloride transport inhibitors.