Effects of dipyrone on the digestive tract

Dipyrone (metamizole), acting through its main metabolites 4-methyl-amino-antipyrine and 4-amino-antipyrine, has established analgesic, antipyretic, and spasmolytic pharmacological effects, which are mediated by poorly known mechanisms. In rats, intravenously administered dipyrone delays gastric emptying (GE) of liquids with the participation of capsaicin-sensitive afferent fibers. This effect seems to be mediated by norepinephrine originating from the sympathetic nervous system but not from the superior celiac-mesenteric ganglion complex, which activates β2-adrenoceptors. In rats, in contrast to nonselective non-hormonal anti-inflammatory drugs, dipyrone protects the gastric mucosa attenuating the development of gastric ulcers induced by a number of agents. Clinically, it has been demonstrated that dipyrone is effective in the control of colic-like abdominal pain originating from the biliary and intestinal tracts. Since studies in humans and animals have demonstrated the presence of β2-adrenoceptors in biliary tract smooth muscle and β2-adrenoceptor activation has been shown to occur in dipyrone-induced delayed GE, it is likely that this kind of receptors may participate in the reduction of smooth muscle spasm of the sphincter of Oddi induced by dipyrone. There is no evidence that dipyrone may interfere with small bowel and colon motility, and the clinical results of its therapeutic use in intestinal colic appear to be due to its analgesic effect.

Residence of liquids in the infra-junctional portion of the proximal stomach in patients with gastroesophageal reflux disease

Patients with gastroesophageal reflux disease may have disturbances of gastric motility, which could play a role in the pathophysiology of the disease. Recent studies have suggested that the gastric region just below the gastroesophageal junction may have a distinct physiological behavior. We determined whether patients with gastroesophageal reflux disease have abnormal residence of food in the infra-junctional portion of the stomach after ingesting a liquid nutrient meal. Fasted adult patients with reflux disease (N = 11) and healthy volunteers (N = 10) ingested a liquid meal (320 ml; 437 kcal) labeled with 99m technetium-phytate and their total gastric emptying half-time and regional emptying from the stomach infra-junctional region were determined. In 8 patients, episodes of postprandial acidic reflux to the esophagus were measured for 2 h using pH monitoring. There were no differences between reflux patients and controls regarding total gastric emptying time (median: 68 min; range: 39-123 min vs 65 min and 60-99 min, respectively; P > 0.50). Food residence in the infra-junctional area was similar for patients and controls: 23 percent (range: 20-30) vs 27 percent (range: 19-30 percent; P = 0.28) and emptying from this area paralleled total gastric emptying (Rs = 0.79; P = 0.04). There was no correlation between residence of food in the infra-junctional area and episodes of gastroesophageal reflux (Rs = 0.06; P = 0.88). We conclude that it is unlikely that regional motor disturbances involving the infra-junctional region of the stomach play a relevant role in the pathogenesis of acidic gastroesophageal reflux.

Postprandial symptoms in dysmotility-like functional dyspepsia are not related to disturbances of gastric myoelectrical activity

Gastric dysrhythmias, such as tachy- or bradygastria, have been reported in patients with functional dyspepsia (FD), but their role in symptom production is uncertain. It is also not known whether gastric dysrhythmias in these patients can be elicited by physiological gastric distension with a meal. We investigated the relationships between symptoms after ingestion of different volumes of water following a test meal and gastric dysrhythmias in FD patients. Fourteen patients with dysmotility-like FD and 13 healthy volunteers underwent paired electrogastrography (EGG) studies. Fasted subjects ingested 150 ml of yoghurt with either 150 ml (low volume) or 300 ml (high volume) water in random order. Fasting and fed EGGs with monitoring of symptoms were performed in both studies. Ten FD patients (71.4 percent) reported upper abdominal discomfort and bloating after the low volume meal, but only one (7.1 percent) presented an abnormal EGG (dominant frequency in the 2-4-cpm range: 58 percent). Following the high volume meal, 7 patients (50 percent) had symptoms, but none had EGG abnormalities. No significant differences were found between FD patients and controls for any of the EGG variables, in any test. In FD patients with postprandial symptoms, the percentage of the EGG dominant frequency in the normal range (median, 84.6 percent; range, 76.0-100.0 percent) was similar (P > 0.20) to that in those without symptoms (88.5 percent; 75.0-100.0 percent). We conclude that disturbances of gastric myoelectrical activity are unlikely to play a role in the origin of postprandial upper abdominal discomfort and bloating in dysmotility-like FD.

Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

Gastric antral dysmotility has been implicated in the pathogenesis of indomethacin-induced gastric damage, but the relationship between gastric motor abnormalities and mucosal lesions has not been extensively studied. We investigated whether changes in gastric tone and gastric retention correlate with mucosal lesions and neutrophil migration in indomethacin-induced gastric damage in rats. Indomethacin, either 5 or 20 mg/kg (INDO-5 and INDO-20), was instilled into the stomach, and then gastric damage, neutrophil migration, gastric tone and gastric retention were assessed 1 or 3 h later. Gastric damage was calculated as the sum of the lengths of all mucosal lesions, and neutrophil migration was measured by assaying myeloperoxidase activity. Gastric tone was determined by a plethysmometric method, and gastric retention of either saline or Sustacal« was evaluated by a scintigraphic method. Gastric damage was detectable 3 h after either INDO-5 or INDO-20, but not after 1 h. Neutrophil migration was significantly higher 3 h after INDO-20 as compared with INDO-5 or control group, but not after 1 h. Values of gastric tone 1 and 3 h after either INDO-5 (1 h = 1.73 ± 0.07 ml; 3 h = 1.87 ± 0.03 ml) or INDO-20 (1 h = 1.70 ± 0.02 ml; 3 h = 1.79 ± 0.03 ml) were significantly lower than in controls (1 h = 1.48 ± 0.05 ml; 3 h = 1.60 ± 0.06 ml). Gastric retention of saline was higher 1 h after INDO-5 (58.9 ± 3.3 percent) or INDO-20 (56.1 ± 3.1 percent) compared to control (45.5 ± 1.7 percent), but not after 3 h. There were no differences concerning gastric retention of Sustacal« between the various groups. Indomethacin induced decreased gastric tone and delayed gastric emptying, which precede mucosal lesion and neutrophil infiltration. These results indicate that there is no relationship between these gastric motor abnormalities and mucosal lesion in indomethacin-induced gastropathy

Inhibition of gastric emptying and intestinal transit in anesthetized rats by a Tityus serrulatus scorpion toxin

The effects of a fraction (T1) of Tityus serrulatus scorpion venom prepared by gel filtration on gastric emptying and small intestinal transit were investigated in male Wistar rats. Fasted animals were anesthetized with urethane, submitted to tracheal intubation and right jugular vein cannulation. Scorpion toxin (250 Ág/kg) or saline was injected iv and 1 h later a bolus of saline (1.0 ml/100 g) labeled with 99m technetium-phytate (10 MBq) was administered by gavage. After 15 min, animals were sacrificed and the radioactivity remaining in the stomach was determined. Intestinal transit was evaluated by instillation of a technetium-labeled saline bolus (1.0 ml) through a cannula previously implanted in the duodenum. After 60 min, the progression of the marker throughout 7 consecutive gut segments was estimated by the geometric center method. Gastric retention of the liquid test meal in rats injected with scorpion toxin (median: 88 percent; range: 52-95 percent) was significantly higher (P<0.02) than in controls (54 percent; 21-76 percent), an effect which was not modified by gastric secretion blockade with ranitidine. The progression of the isotope marker throughout the small intestine was significantly slower (P<0.05) in rats treated with toxin (1.2; 1.0-2.5) than in control animals (2.3; 1.0-3.2). Inhibition of both gastric emptying and intestinal transit in rats injected with scorpion toxin suggests an increased resistance to aboral flow, which might be caused by abnormal neurotransmitter release or by the local effects of venom on smooth muscle cells

Lower density of antral somatostatin-immunoreactive cells in the digestive form of chronic Chagas' disease

Patients with the digestive form of chronic Chagas' disease exhibit abnormally increased gastrin release, possibly caused by antral gastrin cell (G cell) hyperfunction. In order to identify the mechanisms underlying this abnormality, we used an immunohistochemical method to assess the population of antral somatostatin-producing cells (D cells) in chagasic patients, since somatostatin is known to be the main inhibitory factor of gastrin secretion. Samples (N = 11) of endoscopic antral biopsies taken from 16 Chagas' disease patients and 13 control subjects were studied. Antral D and G cell populations were determined by an immunohistochemical technique using highly specific antibodies against somatostatin and gastrin. There was no significant difference between Chagas' disease and control groups regarding G cell population (number of cells/mm reported as median (range): 70.0 (23.7-247.0) vs 98.1 (52.7-169.4), P>0.10). In contrast, the number of antral D cells in Chagas' disease patients was significantly lower than in controls (l6.4 (6.9-54.4) vs 59.3 (29.6-113.8), P<0.05). Chronic superficial gastritis and infection with Helicobacter pylori were more frequent in chagasic patients than in controls, but there was no demonstrable association between these factors and the reduction of the number of antral D cells. These data suggest that reduction in the number of antral somatostatin-producing cells, which should lead to reduced inhibition of gastrin cell activity, may play a role in the increased gastrin secretion observed in Chagas' disease patients.

Scintigraphic study of the gastrointestinal transit of a liquid meal in patients with chronic chagas'disease

Gastric emptying and small bowel transit of a liquid meal (sotonic dextrose) were assessed by a scintigraphic technique in 16 patients with Chagas'disease involving the esophagus and/or the colon, including one case with megajejunum, and in 10 control subjects. Initial gastric emptying was faster in the Chagas'disease group than in controls (gastric retention at 15 min, median and (range): 52% (15-86) vs 71% (43-97), P<0.01) although there was no significant difference in total gastric emptying (T1/2:20 min (4-132) vs 31 min (13-280), P>0.05). Both the front (time to reach the proximal small bowel: 2.5 min (2.5-8) vs 15 min (5-40), P<0.01) and the bulk of the meal (geometric center values at 15 min:1.8(1.2-2.4) vs 1.6(1.2-1.8), P<0.05) travelled faster through the proximal small bowel in Chagas'disease patients than in control subjects. There was no difference between the two groups concerning the time taken by the front of the meal to arrive to the caecum (110 min (15-180) vs 90 min (60-140), P>0.20), but a precise delineation of this region was possible in only less than half of the patients and controls. in the patient with megajujunum, a remarkable delay in the intestinal progression of the liquid meal was found. These results suggest that the diffuse lesion of the enteric nervous system in chronic Chagas'disease mainly affects the controlnof gastric emptying and leads to accelerated proximal small bowel transit of a liquid meal. Impairment of the intestinal progression of the liquid meal seems to occur only inn assocaition of the small bowel

Use of isosorbide dinitrate for the symptomatic treatment of patients with Chagas' disease achalasia: a double-blind, crossover trial

1. A randomized, double-blind, placebo-controlled trial was carried out to determine the efficacy of isosorbide dinitrate (ISD) on diasphagia in patients with Chagasic achalasia. 2. Twenty-three patients with Chagas' disease and dysphagia entered the study ans 20 (87%) complelted the two 7-day treatment periods. Subjects were given either 5 mg ISD (12 patients) or placebo (11 patients) by the sublingual route for the first 7 days. On the 8 th day, patients crossed over and began another 7-days period during which they received the opposite, identical-appearing tablets. 3. Scores attributed by uniformed investigators for the frequency and severity of dysphagia were signidicantly lower (P,0.05) following ISD treatment than after the placebo period or for the pretreatment condition. A significantly higher degree of improvement of dysphagia was experienced by the patients during ISD treatment than during the placebo period. Fourteen patients experienced meal-related headaches during ISD, but not placebo treatment. The extent of improvement in general well-being due to ISD was the same when the drug given in the first or second test period. 4. Our results indicate that ISD, 5 mg by the sublingual route, is effective in alleviating dysphagia in patients with Chagasic achalasia but its usefulness is limited by the high rate of headache as a side effect