(1/285) Effect of motilin on the lower oesophageal sphincter.
The effect of motilin on lower oesophageal sphincter (LES) pressure has been studied in unanesthetised specially trained dogs using an infusion manometric technique. Motilin produced significant rises in resting pressure and contractions of the LES after doses ranging from 0-009 mug/kg to 0-05 mug/kg. Doses greater than 0-05 mug/kg resulted in repetitive high amplitude contractions. Atropine 30 mug/kg completely abolished the effect of the lower doses of motilin. Higher doses of motilin in atropinised dogs still caused a small rise in baseline pressure and contractile activity still appeared. Hexamethonium 2 mg/kg resulted in both a diminished rise in LES pressure and the disappearance of contractions after motilin. Hexamethonium and atropine together completely abolished the LES response to motilin. We conclude that motilin increases LES pressure by acting on preganglionic cholinergic neurones to release acetylcholine which excites other cholinergic neurones supplying the circular muscle of the LES. (+info)
(2/285) Preliminary studies of pharmacological antigonism of anaphylaxis in the horse.
Systemic anaphylaxis was induced in seven groups of ponies. Systemic hypotension, pulmonary hypotension, and apnea were observed in the control group. Suppression of anaphylaxis was achieved most efficiently with sodium meclofenamate followed by acetylsalicylic acid and diethylcarboamazine. Tripelennamine and methysergide reduced anaphylaxis minimally and burimamide not at all. The findings suggest that histamine and serotonin are of relatively low significance in equine anaphylaxis whereas kinins, prostaglandins and slow reacting substance may be more important. (+info)
(3/285) Perception of bronchoconstriction and bronchial hyper-responsiveness in asthma.
The inter-relationship between the perception of bronchoconstriction, bronchial hyper-responsiveness and temporal adaptation in asthma is still a matter of debate. In a total of 52 stable asthmatic patients, 32 without airway obstruction inverted question markforced expiratory volume in 1 s (FEV(1))/vital capacity (VC) 84.1% (S.D. 7.9%), and 20 with airway obstruction [FEV(1)/VC 60% (4%)], we assessed the perception of bronchoconstriction during methacholine inhalation by using: (i) the slope and intercept of the Borg and VAS (Visual Analog Scale) scores against the decrease in FEV(1), expressed as a percentage of the predicted value; and (ii) the Borg and VAS scores at a 20% decrease in FEV(1) from the lowest post-saline level (PB(20)). Bronchial hyper-responsiveness was assessed as the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)FEV(1)). The reduction in FEV(1) was significantly related to the Borg and VAS scores, with values for the group mean slope and intercept of this relationship of 0.13 (S.D. 0.08) and -1.1 (3.02) for Borg, and 1.5 (1.19) and -12.01 (35) for VAS. PB(20) was 3 (1.75) with Borg scores and 34.6 (20.5) with VAS scores. Compared with the subgroup without airway obstruction, the obstructed subgroup exhibited similar slopes, but lower Borg and VAS intercepts. For similar decreases in FEV(1) (5-20% decreases from the lowest post-saline values), the Borg and VAS scores were lower in the non-obstructed than in the obstructed subgroup. PC(20)FEV(1) was significantly related to both Borg PB(20) and VAS PB(20) when considering all patients. When assessing the subgroups, PC(20)FEV(1) was related to Borg PB(20) and VAS PB(20) in the non-obstructed subjects, but not in the obstructed subjects. In neither subgroup was the log of the cumulative dose related to the Borg and VAS scores at the end of the test. We conclude that, unlike in previous studies, the ability to perceive acute bronchoconstriction may be reduced as background airflow obstruction increases in asthma. Bronchial hyper-responsiveness did not play a major role in perceived breathlessness in patients without airway obstruction, and even less of a role in patients with obstruction. The cumulative dose of agonist did not appear to influence the perception of bronchoconstriction. (+info)
(4/285) Alterations in secretory patterns following antrectomy in rats with Pavlov pouches.
1. In conscious rats provided with Pavlov pouches, with the antrum retained or resected,the gastric secretory response to various stimuli has been studied. Each acid secretory response was related to that obtained with maximal doses of methacholine and histamine in combination, presumed to reflect the maximal secretory capacity of the mucosa. 2. Three weeks after the operation, the maximal acid secretory capacity was 60 percent lower in the antrectomized than in the intact Pavlov pouch rats; the difference was still larger at 6 weeks and 3-5 months, owing to a gradual increase in the rats with the antrum retained. 3. Antrectomy reduced interdigestive secretion of acid to the same degree as the concomitant reduction in maximal secretory capacity. 4. Acid secretion in response to a maximal infusion of pentagastrin was reduced by about 50 percent at 3 and about 65 percent at 6 weeks after antrectomy. No significant difference was, however, noted between the antrectomized and intact rats when the responses were related to the maximal secretory capacity. The dose response curve to pentagastrin revealed a redcued responsiveness to submaximal doses of this agent following antrectomy. 5. The maximal acid secretory response to histamine was reduced after antrectomy, although the sensitivity to submaximal infusions of histamine appeared to be increased. 6. The mean secretroy output to 2-deoxy-D-glucose was reduced by about 65 percent and that to food by about 85 percent following antrectomy. 7. After antrectomy a background infusion of pentagastrin enhanced the secretory responses to 2-deoxy-D-glucose and to food but did not restore the responses to the levels in the intact rats. The feeding responses as related to the maximal secretory capacity were, however, similar in the two groups on infusing pentagastrin in the antrectomized rats. 8. Interdigestive secretion of pepsin was reduced by about 60 percent after antrectomy, while the peak response to 2-deoxy-Dglucose was about twice the interdigestive level in both groups. Pepsin secretion in response to food showed an increased secretion above the interdigestive level of longer duration in the antrectomized than in the intact Pavlov pouch rats. 9. The irreversibily reduced responsiveness of the gastric mucosa after antrectomy is discussed in relation to known morphological and biochemical changes. (+info)
(5/285) Bronchial hypersensitivity to methacholine in monkeys with beta-adrenergic blockade.
In monkeys with beta-adrenergic blockade caused by administration of propranolol, we found that the conductance of the total respiratory system markedly decreased following intravenous administration of methacholine. The presence of beta-adrenergic blockade was judged from inotropic effect on the heart, levels of blood glucose and lactic acid, and the reaction of eosinophils after adrenalin injection. (+info)
(6/285) Influence of various factors and drugs on cysteamine-induced duodenal ulcers in the rat.
The cysteamine-induced duodenal ulcer reported by Selye et al. was investigated and the optimum conditions for the production of ulcers in rats were established. A single subcutaneous administration of cysteamine between 200 and 500 mg/kg produced ulceration in a dose-dependent manner in the duodenum within 18 hr. Female and older rats were more susceptible to cysteamine than male and younger ones, respectively. Atropine methylbromide inhibited duodenal ulcers induced by cysteamine dose-dependently and pyloric ligation immediately prior to cysteamine dosing completely inhibited ulceration. Tegragastrin or bethanechol increased the severity of cysteamine-induced ulceration. These data suggest that gastric juice may play an important role in the pathogenesis of cysteamine-induced ulcers. The present study provided an excellent animal model for studying the mechanism of duodenal ulcers and screening of antiulcer agents. (+info)
(7/285) Oropharyngeal angioedema induced by inhaled histamine.
Inhaled histamine used to measure airway responsiveness produces some side effects more frequently than does methacholine. It is possible that the inhaled histamine induces the side effects in asthmatics with increased end organ responsiveness to histamine. A 56-yr-old woman with chronic idiopathic angioedema presented with asthma-like symptoms. Methacholine challenge test was performed, with a negative result. Five days later, histamine inhalation test was done. FEV1 fell by 37% after inhalation of histamine concentration of 8 mg/mL. Immediately thereafter, severe angioedema on face, lips, and oropharyngeal area, foreign body sensation at throat, and hoarseness occurred. To assess end organ responsiveness to histamine, skin prick tests with doubling concentrations of histamine (0.03-16 mg/mL) were carried out on the forearm of the patient and six age- and sex-matched asthmatic controls. The wheal areas were measured. The patient showed greater skin responses than the controls. Regression analysis showed that the intercept and slope were greater than cut-off levels determined from six controls. The patient showed an increased skin wheal response to histamine, indicating the enhanced end organ responsiveness to histamine, which is likely to contribute to the development of the oropharyngeal angioedema by inhaled histamine. (+info)
(8/285) Correction of characteristic abnormalities of microtubule function and granule morphology in Chediak-Higashi syndrome with cholinergic agonists.
Chediak-Higashi (CH) syndrome is a genetic disorder of children and certain animal species including the beige mouse. We have previously described a membrane abnormality in CH mouse polymorphonuclear leukocytes (PMH). Whereas normal mouse PMN do not form surface caps with concanavalin A except after treatment with agents such as colchicine that inhibit microtubule assembly, CH mouse PMN show spontaneous cap formation. This capping is inhibited by 3',5 cyclic guanosine monophosphate and by the cholinergic agonists carbamylcholine and carbamyl beta-methylcholine that increase 3',5' cyclic guanosine monophosphate generation. These data suggested that microtubule function may be impaired in CH syndrome perhaps secondary to an abnormality in 3',5' cyclic guanosine monophosphate generation. The cholinergic agonists were also shown to prevent development of the giant granules that are pathognomonic of CH syndrome in embryonic fibroblasts isolated from CH mice and cultured in vitro. In this report it is shown that an extreme degree of spontaneous concanavalin A cap formation is also characteristic of peripheral blood PMN from two patients with CH syndrome. This indicates an abnormality of microtubule function in CH syndrome in man. 3',5' cyclic guanosine monophasphate, carbamylcholine, and carbamyl beta-methylcholine reduce spontaneous capping in CH cells. In addition, it is shown that monocytes isolated from the patients' blood and incubated in tissue culture generate a large complement of abnormal granules. When the same cells mature in vitro in the presence of carbamylcholine or carbamyl beta-methylcholine, the proportion of cells containing morphologically normal granules is significantly increased. These responses can be reproduced in vivo in the beige (CH) mouse. Animals treated for 3 wk and longer with carbamylcholine or carbamyl beta-methylcholline show normal granule morphology and a normal degree of concanavalin A cap formation in peripheral blood PMN leukocytes. (+info)