Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs

Hamamoto, Junji, Hirotsugu Kohrogi, Osamu Kawano,Hajime Iwagoe, Kazuhiko Fujii, Nahomi Hirata, and Masayuki Ando.Esophageal stimulation by hydrochloric acid causes neurogenicinflammation in the airways in guinea pigs. J. Appl.Physiol. 82(3): 738-745, 1997.Toinvestigate whether tachykinins are released in the airways in responseto stimulation of the esophagus, we studied the airway plasmaextravasation induced by intraesophageal HCl in the presence or absenceof neutral endopeptidase inhibitor phosphoramidon and NK₁-receptor antagonist FK-888 inanesthetized guinea pigs. The airway plasma leakage wasevaluated by measuring extravasated Evans blue dye in the animalspretreated with propranolol and atropine. Infusion of 1 N HCl into theesophagus significantly increased plasma extravasation in the trachea.Phosphoramidon significantly potentiated plasma extravasation in thetrachea and main bronchi, whereas FK-888 significantly inhibited that extravasation in a dose-related manner. In the capsaicin-treated animals, airway plasma extravasation was completely inhibited even inthe presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilateral vagotomized animals. These results suggest that1) tachykinin-like substances arereleased to cause plasma extravasation in the airways as a result ofintraesophageal HCl stimulation and2) there are neural pathwayscommunicating between the esophagus and airways, including the vagusnerve.

     

Antifungal therapy of dermatophytosis in guinea pigs and congenitally athymic rats

Guinea pigs and athymic nude (RNU/RNU) rats were used to assess the efficacy of three orally administered antifungal agents — Tolciclate, Tolnaftate, and Ketoconazole — against Trichophyton mentagrophytes dermatophytosis. All three antifungal agents inhibited the test strain of T. mentagrophytes in vitro. Antifungal agents were tested in intervention (oral therapy started 5 days after challenge) or prophylaxis (oral therapy started 5 days before challenge) protocols. Oral treatment of dermatophytosis on guinea pig skin demonstrated that Tolciclate and Tolnaftate alleviated clinical symptoms and shortened the duration of the dermatophytosis, in comparison to nontreated controls. Assessment of antifungal efficacy in the guinea pig model was time consuming (30–35 days) and variability in the duration and severity of clinical symptoms on guinea pig skin was common.Oral therapy of chronically infected athymic rats demonstrated that Tolciclate, Tolnaftate, and Ketoconazole were effective antifungal agents in vivo. Obvious improvement in clinical symptoms of dermatophytosis (i.e. less erythema and fewer lesions) was evident with all three antifungal agents within 10 days of starting oral therapy. By day 20, athymic rats that were treated with either Tolciclate or Ketoconazole showed marked clinical improvement of the chronic dermatophytosis.Chronically infected athymic rats, which lack thymus matured T-cells, are a promising new model to evaluate the efficacy of antifungal agents by culture, histology, and visual observations of clinical symptoms.     

Fever induction by localized subcutaneous inflammation in guinea pigs: the role of cytokines and prostaglandins.

In guinea pigs, dose-dependent febrile responses can be induced by injection of a high (100 micro g/kg) or low (10 micro g/kg) dose of bacterial lipopolysaccharide (LPS) into artificial subcutaneously implanted Teflon chambers. In this fever model, LPS does not enter the systemic circulation from the site of localized tissue inflammation in considerable amounts but causes a local induction of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6), which can be measured in lavage fluid collected from the chamber area. Only in response to the high LPS dose, small traces of TNF are measurable in blood plasma. A moderate increase of circulating IL-6 occurs in response to administration of both LPS doses. To investigate the putative roles of TNF and prostaglandins in this fever model, a neutralizing TNF binding protein (TNF-bp) or a nonselective inhibitor of cyclooxygenases (diclofenac) was injected along with the high or low dose of LPS into the subcutaneous chamber. In control groups, both doses of LPS were administered into the chamber along with the respective vehicles for the applied drugs. The fever response to the high LPS dose remained unimpaired by treatment with TNF-bp despite an effective neutralization of bioactive TNF in the inflamed tissue area. In response to the low LPS dose, there was an accelerated defervescence under the influence of TNF-bp. Blockade of prostaglandin formation with diclofenac completely abolished fever in response to both LPS doses. In conclusion, prostaglandins seem to be essential components for the manifestation of fever in this model.     

The effect of urine from castrated male or female guinea pigs and rats on the estrous cycle of guinea pigs and rats, respectively]

A 24-hour reduced cycle duration was observed in 5-day cyclic female rats exposed to the odor of urine from male or female castrated rats. A decrease in the duration of the period of vaginal closure, ranging from 2 to 5 days, was observed in female guinea pigs exposed to the odor of urine from male or female castrated guinea pigs. The pheromonal activity of urine in both species was concluded to be no dependent upon the gonadal function.     

Site of intestinal absorption of ascorbic acid in guinea pigs and rats

The site of absorption of ascorbic acid by the small intestine was studied $\text{in vivo}$ in guinea pigs, normal and hypophysectomized rats after oral application of ¹⁴C-ascorbic acid. A species-specific difference was revealed. The site of absorption in the guinea pig was located in the duodenal and proximal small intestinal wall, whereas the rat showed highest absorption in the ileum. Hypophysectomy in rats caused a shift of the absorption site from the ileum to the jejunum. No absorption was observed in the duodenum and ileum. A regulatory role of the pituitary gland in the absorption of ascorbic acid by the small intestine is discussed.     

Gastric antisecretory and antiulcer activity of oxytocin in rats and guinea pigs.

The effect of oxytocin (1 mg/kg s.c) on gastric acid secretion and on different experimentally induced gastric and duodenal ulcers was studied. The acute gastric ulcer models used were pylorus ligation, indomethacin, ethanol and histamine induced acute gastric ulcers. Chronic gastric ulcers were induced using acetic acid and duodenal ulcers by cysteamine hydrochloride. Oxytocin showed significant antisecretory and antiulcer activity in pylorus ligated rats. Similarly oxytocin reduced the ulcer index in histamine induced gastric ulcers in guinea pigs and cysteamine induced duodenal ulcers in rats. The antiulcer and antisecretory effect was comparable to that of ranitidine (50mg/kg, i.p) though less in intensity. However, it did not show any gastric cytoprotective effect in ethanol and indomethacin induced ulcer models but ranitidine showed protection (p<0.05) in later model. Oxytocin enhanced gastric ulcer healing in acetic acid induced chronic gastric ulcer model. The reversal of oxytocin effect by atosiban, an oxytocin receptor antagonist indicates a role for oxytocin receptors. The antiulcer activity of oxytocin can be attributed to its antisecretory effect.