Different neurotransmitter systems are involved in the development of esophageal achalasia.

Clinical and pharmacological evidence suggests that several neurotransmitters are involved in the control of the esophageal motility; in fact, besides the well known cholinergic and sympathetic innervation, Vasoactive Intestinal Polypeptide (VIP)-containing fibers as well as dopamine (DA)-containing nerve endings have been identified within the esophageal wall. Lower Esophageal Sphincter (LES) achalasia is a neuromuscular disorder characterized by the absence of peristalsis in the body of the esophagus and by the failure of the LES to relax in response to swallowing. Stimulation of both VIP receptors and D-2 DA receptors induce a decrease in LES pressure, while D-1 receptors mediates LES contractions. In the present study we show that both VIP and DA system is disregulated in LES achalasia. In particular, this disease is associated not only with the lack of VIP nerves in the LES, but also with a failure in the responsiveness of postsynaptic receptors to VIP stimulation. Furthermore, we demonstrate a selective functional loss of the D-2 DA receptor component, without changes in the D-1 DA receptor mediated responses.

Cytometric ploidy and proliferative activity in colorectal carcinoma.

Thirty cases of colorectal carcinoma have been evaluated for proliferative activity with the monoclonal antibody Ki 67 and with flow cytometry for ploidy, DNA index and the S-phase fraction. In the series, 30% of tumours were strictly aneuploid, 23.8% tetraploid and 45% diploid: "non diploid" cases accounted for 53.8%. The mean comprehensive values of DNA index, percent S-phase and Ki 67 positive fraction were 1.4%, 11.5% and 50%, respectively. The parameters considered showed no statistically significant correlation with each other or with the common histo-pathologic parameters, such as grading and staging. The prevalent prognostic importance of ploidy compared to DNA index is emphasized, and particular attention is paid to diploid cases with a high growth fraction (S-phase fraction), which could make up an "at risk" category. Therefore, we attempted to identify subsets, within groups of the same histologic stage, with a different evolutive significance in relation to DNA content, percentage of positivity to Ki 67, S-phase fraction and ploidy. With such a multi-parametric approach, particular groups of patients at risk could be defined, which are perhaps more sensitive to specific support therapies.

Opposing roles for D-1 and D-2 dopamine receptors in the regulation of lower esophageal sphincter motility in the rat.

In the present study we have identified biochemically DA receptors in rat Lower Esophageal Sphincter (LES) and have identified their role in the control of the sphincter motility. Dopamine (DA) both stimulated and inhibited cyclic AMP formation in rat LES; the pharmacological characterization of these effects indicated that they were mediated by D-1 and D-2 receptors, respectively. The results obtained with LES helical strips showed that DA plays both inhibitory and stimulatory effects on the sphincter function; the pharmacological characterization with selective D-1 and D-2 agonists and antagonists strongly suggested that D-1 receptors are involved in LES contraction, while D-2 receptors mediate the relaxation of the sphincter. The same results were obtained by measuring intraluminal LES pressure in anesthetized rats. The selective D-1 agonist fenoldopam (40 micrograms/kg, i.v.) increased the LES pressure; on the other hand bromocriptine (10 micrograms/kg, i.v.), which preferentially interacts with D-2 receptors, induced a decrease of the resting LES pressure.

[DNA index of colorectal carcinoma and follow-up]. / DNA index del carcinoma colon-rettale e follow-up.

In relation to DNA index we have studied 18 cases of differently evoluted carcinoma of the colon, some incoherently (8) other in agreement (10) with staging. Static and flow cytometric techniques have been employed, the first by means of densitometric study on paraffin sections with the Feulgen method, the second based on application of Hedley method on paraffin included material. DNA content, pressed by the DNA index, is inversely proportional to survival with similar results in both techniques, from which the possible prognostic significance is argued.

Evidence for the presence of both D-1 and D-2 dopamine receptors in human esophagus.

Clinical and pharmacological evidence suggested that dopamine is involved in the control of esophageal motility. The present study was designed to determine whether or not dopamine receptors are present in human esophagus. With this aim we measured adenylate cyclase activity as a biochemical index of dopamine receptor function in esophageal specimens taken from five patients during surgery for upper esophageal carcinoma. The selective D-1 agonist fenoldopam stimulated cAMP formation in the lower esophageal sphincter, but not in the esophageal body; this effect was prevented by the selective D-1 antagonist SCH 23390 and by d-butaclamol. Bromocriptine, a selective D-2 stimulator, inhibited adenylate cyclase activity in the lower esophageal sphincter, an effect blocked by the D-2 antagonist (-)sulpiride. No effects of bromocriptine were found in the esophageal body. These data indicate that both D-1 and D-2 receptors are present in the lower esophageal sphincter, but not in esophageal body and emphasize the role of dopamine in the regulation of esophageal function.