No abstract

To study whether or not the autonomic nervous system influences the defense mechanisms of the gastric mucosa, groups of Sprague-Dawley rats were given stimulants and inhibitors of the different components of the vagus and celiac nerves before administration of absolute or 70% w/v ethanol. The effects of vagotomy and sympathectomy on "adaptive cytoprotection" were studied, as were the effects of blocking the muscarinic receptors and stimulation of beta-adrenergic receptors. We found that: (1) cholinomimetic agents and norepinephrine make the damage caused by 70% ethanol worse; (2) atropine is the only agent that fully protects against absolute ethanol; (3) vagotomy and sympathectomy abolish the effects of atropine and adaptive cytoprotection; and (4) beta-adrenergic stimulation replaces conditions that allow adaptive cytoprotection and the protection by anticholinergics. These results suggest that two different reflexes are triggered by ethanol: when low concentrations are given, the beta-adrenergic-mediated effect is prevalent, with protection of the mucosa; when high concentrations are given, the cholinergic-mediated effect is prevalent with damage of the mucosa.

In 1989 there were 151,000 new cases of colorectal carcinoma in the United States. Approximately 50% of these patients will be at risk of developing liver metastases together with other sites of recurrence. However, the liver will be the main site of relapse in only 14,000 patients with colorectal cancer. [1,2,12,15,19]. Approximately 25% of patients with colorectal carcinoma have technically resectable hepatic metastases at the time of operation for primary lesion, and an additional 8-25% will develop metachronous hepatic metastases after primary resection [ 15,251. Recent reported experiences with surgical treatment of metastatic colorectal cancer in the liver seem to indicate that hepatic resection has become more acceptable, safe and effective therapy, and offers today when technically possible, the best prospect of survival in a conspicuous number of patients. For these reasons, although a prospective randomized trial has not been done comparing resection with nonresection, resection seems to give the best hope for cure and actually is the treatment of choice for selected patients. In fact in these patients is reported a significant prolongation of survival compared with those patients with unresectable liver metastases treated only with adjuvant therapy in the form of chemotherapy or radiation therapy.Median survival of resected patients with hepatic metastases has been reported to range from 6-12 months, and for patients with single metastases is reported to range from 4.5-6.2 months to 11 and 21 months [16,22,25,27].The benefits of surgical therapy have been emphasized by different experience, with a 5-year overall survival rate ranging from 2MO%. In a recent multicenter survey a 33% 5-year survival rate was demonstrated in 859 patients resected for hepatic metastases.

Gastric carbonic anhydrase (CA) is believed to play an important role related to cytoprotection, and duodenogastric reflux of bile salts (BS) is suspected of having a causal role in many pathologic conditions. Thus, we decided to investigate the effect of free and conjugated BS on human and rat gastric CA activity. Cholate exerted the most potent inhibitory activity on both human (I50 = 2.24 mM) and rat (I50 = 1.68 mM) gastric CA, followed by glycochenodeoxycholate and taurocholate (I50 = 6.90 mM and 13.67 mM on rat gastric CA). Human and rat whole bile produced 10-90% and 20-40% inhibition of gastric CA of the same species. Since the concentrations of free and conjugated BS tested in this study can be found in the postgastrectomized stomach, our data suggest that inhibition of gastric CA might be one mechanism contributing to the gastric mucosa damage caused by BS refluxing into the stomach after gastric surgery.