Effect of inhaled fluticasone on airway reactivity and 8-Iso-PGF2α in bronchoalveolar lavage fluid of cats

AIM: The objective of the this study was to assess the effect of inhaled fluticasone administrated daily during one or two weeks on bronchial reactivity (BR) and airway inflammation of experimental cats with mild, but persistent lower airway inflammation. METHODS: Five European shorthair cats were investigated before (Pre) and after a one-week (Flu-1 W) and or two-week     

Alterations of colonic motility after oral administration of prostaglandin E1 analogue misoprostol in man

This study describes the motor changes observed in human colon under normal feeding schedule, after administration of a single oral does of misoprostol, a PGE₁ synthetic analogue. Fourteen patients (3 men, 11 women, mean age 45±7 years), with chronic abdominal pain but without any detectable organic digestive disease were studied. The colonic motor activity was recorded by endoluminal electromyography during 218-h recording sessions over 2 consecutive days. Misoprostol 600 μg or placebo was randomly administered in double-blind manner either on the first or the second day of the recording period. In 8 patients, misoprostol was administered orally 1 h before the dinner (17.30 hours) and in 6 patients at the beginning of the night-time (23.00hours). Meals were standardized and scheduled during the whole recording session in the same way for all patients. After placebo, colonic response to feeding was characterized by an increase in colonic motor activity mainly concerning the percentage of time occupied by long spike bursts (LSBs =+232%) and migrating long spike bursts (MLSBs =+214%) (p < 0.05). Short spike burst activity (SSBs) was not affected by feeding. Administered before the meal, misoprostol (600 μg) strongly reduced percentage of time occupied by the LSBs activity during post-cibal period (-46%) when compared to placebo (P < 0.01). On the contrary, MLSBs and SSBs activities were similar in post-prandial period after placebo and misoprostol. Administration of misoprostol during the nighttime did not affect the basic colonie myoelectrical pattern when compared to placebo. We conclude that an oral administration of misoprostol before a meal alters the colonic response to feeding, mainly the contractile activity of LSBs.     

Influence of age on rectal tone and sensitivity to distension in healthy subjects

Hypersensitivity to rectal distension is frequently observed in patients with irritable bowel syndrome (IBS). However, few data are available about the influence of age on rectal sensory thresholds and tone. The aim of this study was to measure rectal sensory thresholds and tone with a barostat in 12 healthy subjects (aged 86 +/- 4 years, eight females, four males) as compared with 12 young healthy male controls (26 +/- 1 years). Isobaric phasic distensions were performed in the fasted state (increment of 4 mmHg, steps of 5 min, interval of 5 min). Rectal tone changes were then measured as changes in volume of the barostat bag, the pressure being kept constant. After a baseline recording of 1 h, a 1000-kcal meal was served and the tone recorded until return to baseline. Rectal sensory thresholds were significantly higher in aged subjects. First sensation, sensation of urge to defaecate and sensation of pain were triggered at 21.1 +/- 3.2 mmHg, 30.4 +/- 5.4 mmHg and 40.5 +/- 5.0 mmHg, respectively, in aged subjects, vs 13.3 +/- 4.6 mmHg (P < 0.05), 20.7 +/- 1.0 mmHg (P < 0.001) 31.3 +/- 1.7 mmHg (P < 0.001) in controls. Rectal compliance was not significantly different between the two groups. Mean barostat bag volume was 104 +/- 13 mL in fasting aged subjects and 125 +/- 23 mL in controls (NS). After the meal, the barostat bag volume decreased by 69 +/- 11% during 85 +/- 17 min in aged subjects and 75 +/- 14% during 89 +/- 15 min in young controls (NS). Rectal sensory thresholds triggered by distension are increased in aged healthy subjects while compliance and tone are not different. Age should be considered as a confounding factor when studying rectal sensitivity and further studies in aged patients with IBS should include a group of control subjects within the same range of age as studied patients.     

The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility

Aim: To evaluate the effects of various doses of lintopride, a new 5HT-4 antagonist with moderate 5HT-3 antagonist properties, on oesophageal body and lower oesophageal sphincter (LOS) motility in humans. Methods: Eight healthy male volunteers, mean age 22 (19–28) years, without any history of digestive disease or chest pain, were randomized to three doses of lintopride (0.1, 0.3 and 0.5 mg/kg i.v.) and a placebo at 1-week intervals in a double-blind, crossover study. Oesophageal motility was recorded continuously for 4 h after each dose, using perfused catheters inserted at the level of the LOS and in the body of the oesophagus, at 5, 10 and 15 cm from the LOS. Peristalsis was studied during 10 wet swallows, at 30-min intervals (T₀–T₂₄₀ min). Results: The LOS basal pressure (23.3 ± 2.0 cmH₂O; mean ± s.d.) remained stable after dosing with placebo to T₂₄₀ After lintopride, LOS basal pressure increased significantly vs. placebo (AUC comparison: 0.1 mg/kg, P= 0.036; 0.3 mg/kg, P= 0.027; 0.5 mg/kg, P= 0.052). In contrast, the duration and extent of LOS relaxation after swallowing was not affected by any of the three doses of lintopride. The amplitude of peristaltic waves in the oesophagus increased significantly at T₃₀ after lintopride 0.3 mg/kg (34.5 cmH₂O, P= 0.020) and 0.5 mg/kg (32.5 cmH₂O, P=-0.027), at T₆₀ after 0.3 mg/kg (48.8 cmH₂O, P= 0.0009) and 0.5 mg kg (29.1 cmH₂O, P= 0.029) and at T₆₀ after 0.3 mg/kg (34.5 cmH₂O, P= 0.0018). Conclusions: Lintopride significantly increased the LOS basal tone without affecting LOS physiological relaxation after swallowing. Peristaltic waves were also enhanced by lintopride.     

Broncho-mediastinal fistula following perforation of the oesophagus

Abstract We present a 63-year old female with mediastinitis following an esophageal perforation, possibly favoured by an oesophageal motility disorder and the use of non-steroidal anti-inflammatory drugs, who developed a broncho-mediastinal fistula in the left main bronchus. She was successfully treated with intravenous antibiotics, a cervical oesophagostomy and secondary isoperistaltic coloplasty.     

Effect of various doses of erythromycin on colonic myoelectrical activity in IBS patients

Abstract Erythromycin mimics the effects of motilin but its action on colonic motility is still controversial. The aim of this study was to evaluate the effect of intravenous infusions of various doses of erythromycin on colonic motility in patients with irritable bowel syndrome (IBS).
At 09.00 hours, day 1 (D1), an intraluminal probe was introduced up to the right colon in 24 IBS patients with myoelectrical activity recorded for 48 h. Patients were randomised in three groups of eight, receiving either erythromycin 1.5, 3 or 7 mg kg⁻¹. All were investigated as follows: at 09.00 hours, D2, fasted patients were infused with erythromycin in 30 min; at 09.00 hours, D3, glycerol 10 ml was injected intraluminally. Colonic activity was measured 30 min before the infusion started, during and 30 min after it, separately in the left and right colons, and expressed in time occupied during the recording period.
Basal activity was similar in both parts of the colon. During and after erythromycin 1.5 and 3 mg kg⁻¹, colonic activity remained unchanged. Erythromycin 7 mg kg⁻¹ induced a moderate increase in spiking activity (long spike bursts or LSBs + 33%; migrating LSBs or MLSBs + 41%) in the right colon, no change being statistically significant; activities in the left colon were similar to basal level.
During the first 30 min following glycerol injection, mean short spike burst or SSB activity did not change, mean LSB activity increased by seven fold (P = 0.014) and MLSB activity by ten fold (P = 0.023).
Erythromycin at doses from 1.5 to 7 mg kg⁻¹ failed to stimulate colonic motility in IBS patients. By contrast, response to glycerol was strong, suggesting normal colonic responsiveness. Erythromycin stimulatory effects could be limited to the upper gut at least in IBS patients.     

Iloprost: Intracellular Ca2+-dependent Contractile Effect on Isolated Smooth Muscle Cells from Guinea-pig Ileum

Prostaglandin E₂ (PGE₂) and iloprost induced a concentration-dependent contraction of smooth muscle cells isolated from the circular layer of guinea-pig ileum. PGE₂- and iloprost-induced contractions were inhibited by the selective EP₁-receptor antagonist, SCI9220 (1-acetyl-2-(8-chloro-10, 11-dihydrodibenz (b,f) (1,4) oxazepine-10-carbonyl)-hydrazine), indicating the involvement of the EP₁ subtype of the PGE₂ receptor. When cells were incubated for 10 min in the presence of strontium (4 mm L^?1), an inhibitor of the release of Ca²⁺ from intracellular store, the contractile effect of PGE₂ and iloprost was inhibited. In contrast, incubation of cells in Ca²⁺-free medium, Ca²⁺-free medium plus EGTA, or in the presence of nifedipine, an organic Ca²⁺-channel blocker, did not alter the PGE₂- and iloprost-induced contraction. These observations suggest that the myogenic effect of PGE₂ and iloprost on intestinal smooth muscle is dependent on the release of intracellular calcium.