Factors that modify the effects of prostaglandin on diet-induced acute pancreatitis in mice.

Considerable disagreement exists as to whether prostaglandins improve survival in animals with experimental pancreatitis. In prior studies we have demonstrated a beneficial effect of prostaglandin in the choline deficient, ethionine supplemented diet model of acute hemorrhagic pancreatitis. In the present study we have examined the effects of 1) delaying treatment with 16,-16-dimethyl prostaglandin E2 (PGE2) till 24 h after introduction of the diet and 2) exposing animals to the test diet for 3 days instead of 2. Following delayed treatment mortality in the saline control group (57%) was significantly higher on the fourth day compared to the PGE2 treatment group (3%). However, the overall mortality on day 7 was not significantly different from that seen in the control group (43% versus 60%). In the second series of experiments, PGE2 no longer had a beneficial effect if animals were fed the CDE diet for 3 days. We would conclude from this study and others that the ability to demonstrate a protective effect of PGE2 on the pancreas is dependent upon the experimental protocol employed. Thus, the ability to demonstrate this effect is dependent upon the dose and type of prostaglandins employed, the length of exposure to the test diet, and the time at which treatment is started relative to the induction of the pancreatitis.

Effects of prostaglandin and indomethacin on diet-induced acute pancreatitis in mice.

This study was performed to determine the effects of exogenous prostaglandin and a prostaglandin synthetase inhibitor on experimental pancreatitis in mice. An ethionine-supplemented choline-deficient diet was used to induce pancreatitis in 4-6-wk-old Swiss Webster mice. Mice were injected subcutaneously with 16,16-dimethyl prostaglandin E2 (0.1, 1.0, 10 micrograms X kg-1 X day-1), indomethacin (0.05, 0.5, 5 mg X kg-1 X day-1), or saline for 7 days. The ethionine-supplemented choline-deficient diet was introduced 24 h after the first injection, and animals ate the test diet for 48 h. A 55% mortality was observed in control animals (n = 100) treated with carrier alone. Treatment with 10 micrograms X kg-1 X day-1 of 16,16-dimethyl prostaglandin E2 significantly decreased (p less than 0.01) mortality to 12% (n = 100). Improved survival was accompanied by a significant (p less than 0.05) decrease in the pancreatic content of free chymotrypsin and a decrease in histologic damage. Treatment with 5 mg X kg-1 X day-1 of indomethacin (n = 30) significantly (p less than 0.01) increased mortality in diet-treated rats from a control rate of 55% to 100%. These studies demonstrate a protective effect of prostaglandin on the pancreas and suggest a role for endogenous prostaglandins in the pathophysiology of pancreatitis.

Beneficial effect of pancreatic polypeptide in experimental pancreatitis.

Two animal models have been employed to examine the role of pancreatic polypeptide, a potent and selective inhibitor of pancreatic exocrine secretion, in the treatment of acute pancreatitis. In one model pancreatitis was induced by feeding young female Swiss Webster mice an ethionine-supplemented, choline-deficient diet for 48 hr. Animals (N = 30 per group) were injected subcutaneously every 8 hr for 7 days with pancreatic polypeptide (0, 2, 20, and 200 micrograms/kg/day). Treatment with 20 and 200 micrograms/kg/day pancreatic polypeptide significantly (P less than 0.05) reduced mortality from a control rate of 70% to 42% and 33%, respectively. Treated animals also exhibited significant (P less than 0.05) decreases in pancreatic content of activated chymotrypsin and an improvement in pancreatic histology. Pancreatic polypeptide was effective whether treatment was started before or at the same time the test diet was introduced. In contrast, pancreatic polypeptide failed to protect dogs with acute pancreatitis induced by retrograde injection of the pancreas with bile, which may reflect the rapid and mechanical nature of pancreatic damage in this animal model.

Somatostatin and gastrin release from canine stomach.

Somatostatin and gastrin release into the veins draining the stomach was studied in 27 anaesthetized dogs. Basal somatostatin-like immunoreactivity (SLI) in corpus veins (136 +/- 36 pg/ml) was significantly higher than in antrum veins (83 +/- 20 pg/ml; p less than 0.05) and the femoral artery (58 +/- 15 pg/ml; p less than 0.02). During peptone, pH 6.5, perfusion of the stomach, SLI concentration increased significantly in the corpus veins to approximately four times basal and in the antrum veins to three times basal, whereas SLI levels in the peripheral circulation remained constant. Peptone, pH 3.5, and sodium oleate did not stimulate gastric SLI. Gastric distension increased significantly SLI release from the corpus. In gel filtration studies 50%--70% of SLI from gastric vein plasma samples but greater than 90% from femoral artery samples eluted in the void volume of Sephadex G-25 columns. Gastrin secretion was stimulated significantly only by peptone, pH 6.5.

[Inhibition of gastric secretion by i.v. gastric inhibitory polypeptide (GIP) in man (author's transl)]. / Hemmung der Magensekretion durch intervenöses Gastric Inhibitory Polypeptid (GIP) beim Menschen.

Infusions of GIP in man with innervated stomach is only a potent inhibitor of gastric secretion in high pharmacological doses. Cholinergic mechanisms seem to have an influence on the inhibitory effect of GIP on gastric secretion.

Drug-induced stereotypes and asymmetric behaviour after substantia nigra pars posterior (SNPP) lesions in cats.

Apomorphine- (Apo) and amphetamine- (Amph) induced behavioural phenomena were studied in cats which received either 6-hydroxydopamine (6-OHDA) or electrothermic lesions of the posterior part of the substantia nigra (SNPP). In this species, as in rats, both drugs evoked sterotypies (sniffing and head nodding) and an enhancement of locomotor activity. However, distinct differences between the reactions of cats and rats to both drugs were found, the most evident effect being the lack of sterotyped gnawing and licking. By correlating the data on behaviour, the histological examination showing the size and location of the lesions, and the dopamine (DA) content of the corresponding caudate nuclei, it is concluded that the fewer DA-specific neurons lesioned in the SNPP, the more pronounced was the ipsilateral asymmetric behaviour. We suggest, therefore, that the ipsilateral asymmetric behaviour in cats following APO- and AMPH-treatment is due to the destruction of a non-catecholaminergic output.

[The influence of benzoctamine on dopamine and norepinephrine contents in substantia nigra and on the muscle stretch reflex of the cat (author's transl)]. / Der Einfluss von Benzoctamin auf den Dopamin- und Noradrenalin-Gehalt der Substantia nigra und auf die Muskeldehnungsreflexe der Katze.

The concentration of dopamine (DA) and norepinephrine (NE) are decreased to a maximum of 40% and 20%, respectively, in the substantia nigra of precollicular and prenigral decerebrated cats previously treated with benzoctamine (Tacitin) (0.7 mg/kg i.v.), while the tyrosine-hydroxylase and MAO activities remain unchanged. Muscle stretch reflexes recorded simultaneously showed a significant decrease of stretch tension which is evoked by a clear reduction of Ia discharges of the primary muscle spindle afferents. It would appear that benzoctamine suppresses reflexly evoked gamma-motoneurone discharges.

[Glucose-homeostasis in resection and non-resection procedures of the stomach]. / Glucose-Homeostase bei resezierenden und nicht resezierenden Verfahren am Magen.

Antrectomy or truncal vagotomy with pyloroplasty induces an abnormal alimentary hyperglycemia after ingestion of oral glucose. Low doses of secretin normalize the glucose homeostasis in dogs after antrectomy and truncal vagotomy.

Failure of benzoctamine to influence the activity of rat striatum tyrosine-hydroxylase.

The influence of benzoctamine (Tacitin) on rat striatum tyrosine-hydroxylase was analized. Injection of 100 mg benzoctamine/kg body weight caused no alteration in the tyrosine-hydroxylase activity whilst a decrease of about 60% in the activity was recorded after treatment with a-methyl-p-tyrosine a known inhibitor of tyrosine-hydroxylase. The present results differ from those of Maitre et al. which indicated that benzoctamine inhibited tyrosine-hydroxylase activity.