Role of endogenous serotonin and histamine in the pathogenesis of gastric mucosal lesions in unanaesthetised rats with a single treatment of compound 48/80, a mast cell degranulator.

In unanaethetised rats with a single injection of compound 48/80, a mast cell degranulator (0.75 mg kg-1, i.p.), gastric lesions occurred with increased serum serotonin and histamine levels and reduced gastric mucosal blood flow at 0.5 h after the injection and developed at 3 h. Pretreatment with either cyproheptadine (a serotonin and histamine antagonist) or methysergide (a serotonin antagonist) prevented the formation of gastric mucosal lesions with attenuation of reduced gastric mucosal blood flow at 0.5 h after compound 48/80 injection, while pretreatment with either amitriptyline (a selective inhibitor of histamine release from mast cells), tripelennamine (a histamine H1-receptor antagonist), famotidine (a histamine H2-receptor antagonist) or cimetidine (a histamine H2-receptor antagonist) had no effect. Pretreatment with either cyproheptadine, methysergide, amitriptyline or tripelennamine prevented the development of gastric mucosal lesions at 3 h after compound 48/80 injection, while pretreatment with either famotidine or cimetidine had no effect. These results indicate that in unanaesthetised rats with a single compound 48/80 treatment, acutely released endogenous serotonin causes gastric mucosal lesions, while released endogenous histamine mainly contributes to the lesion development and that gastric acid plays little role in the pathogenesis of the compound 48/80-induced acute gastric lesions.

Evaluation of some prophylactic therapies for the idiopathic headshaker syndrome.

Eighteen horses affected by the idiopathic headshaker syndrome were studied in an owner assessed trial to test the efficacy of some prophylactic therapies. Riding the affected animal with a veil over the nostrils gave varying degrees of temporary relief in three of 10 horses. Local (intra-nasal) corticosteroid therapy was reported to be slightly effective in three of nine horses, but treatment with sodium cromoglycate, systemic corticosteroid, flunixin meglumine and an antihistamine were generally ineffective. Bilateral infraorbital neurectomy provided sustained relief in three of seven horses, but in one of these cases, a reaction at the neurectomy site necessitated another surgical procedure after six months. A fourth horse was reported to be slightly improved after neurectomy. A period of nasal irritation resulting in self-inflicted trauma was a common complication of this surgery.

16,16-Dimethyl prostaglandin E2 aggravates gastric mucosal injury induced by histamine in rats. Possible role of the increased mucosal vascular permeability.

Histamine dihydrochloride (40 or 80 mg/kg, dissolved in 10% gelatin) subcutaneously administered to fasted rats induced few lesions in the gastric mucosa within 4 h. Pretreatment with subcutaneously administered 16,16-dimethyl prostaglandin E2 (dmPGE2; greater than or equal to 10 micrograms/kg) dose-dependently worsened mucosal injury induced by histamine, mostly with severe hemorrhage in the corpus mucosa along the greater curvature, although dmPGE2 alone did not induce any macroscopic damage. The mucosal vascular permeability as measured using Evans blue was slightly but significantly augmented by either dmPGE2 (30 micrograms/kg) or histamine (80 mg/kg) alone, but was markedly increased by histamine in the presence of dmPGE2. The increased vascular permeability occurred within 2 h, and preceded the appearance of hemorrhagic mucosal injury. Both the mucosal injury and the increased vascular permeability caused by histamine (80 mg/kg) in the presence of dmPGE2 (30 micrograms/kg) were significantly reduced by pretreatment with tripelennamine (30 mg/kg) and prednisolone (3 mg/kg), but not affected by atropine sulfate, cimetidine, methysergide, or indomethacin. The stimulation of acid secretion caused by histamine was significantly inhibited by dmPGE2 (30 micrograms/kg). Repeated administration of histamine (40 or 80 mg/kg) in the same area of the stomach in the presence of dmPGE2 (30 micrograms/kg), once or twice daily for 4 days to fed rats, induced more pronounced damage than single-dose treatment. These results suggest that dmPGE2 may aggravate gastric mucosal injury induced by histamine in rats probably due to potentiation of the increased vascular permeability caused by histamine through stimulation of H1-receptors.

Antihistamine selection in patients with allergic rhinitis.

Seven hundred eighty-two patients diagnosed as having either seasonal allergic rhinitis or perennial allergic rhinitis in a solo allergy practice were given five different antihistamine products representing each of the five classes of antihistamines. The following products were evaluated for 2 weeks each: tripelennamine, diphenhydramine, chlorpheniramine, hydroxyzine, and trimeprazine. Symptoms and side effects were graded 0 to 4. The more troublesome side effects, graded 3 or 4, were tabulated. The antihistamine products in order of increasing frequency of significant side effects were: trimeprazine, chlorpheniramine, hydroxyzine, diphenhydramine, and tripelennamine. The order of antihistamine preference by the patients was chlorpheniramine (27%), diphenhydramine (22%), tripelennamine (20%), hydroxyzine (16%), and trimeprazine (14%). Only seven of 758 patients (less than 1%) were unable to find an acceptable antihistamine class. Patients remained on their antihistamine class of first choice 78% of the time after 1 year, 71% after 3 years and 51% after 5 years. The antihistamine pack provides a rational approach to antihistamine selection in patients with allergic rhinitis.

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.

Protection by acetylsalicylic acid and other agents in experimental acute interstitial pneumonia of calves.

In experimental acute interstitial pneumonia caused by Ascaris suum, therapy with aspirin (acetylsalicylic acid) provided symptomatic control of the condition, reducing or abolishing the characteristic "setback". Treatment with antihistamines or antiserotonin agents caused no observable clinical improvements.