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Biomedical subjects

M Del Tacca

Publications and source records attributed to M Del Tacca.

At least 199 records · Page 11Linked to original sources
PubMedDate not supplied

Effects of gonadotropin-releasing hormone (GnRH) on gastric secretion and gastrin release in the dog.

The effects of GnRH on gastric secretion and gastrin release from dogs provided with gastric fistulae and Heidenhain pouches have been investigated. A transient yet significant inhibition of pentagastrin-stimulated secretion from gastric fistulae was observed, while secretion from Heidenhain pouches was unchanged. The maximal inhibitory effect of GnRH on both acid and pepsin secretion stimulated by 2-deoxy-D-glucose was obtained from gastric fistulae. On the contrary, GnRH failed to affect either acid secretion stimulated by bethanechol or acid secretion and gastrin release induced by bombesin. The present results indicate that GnRH possesses an inhibitory action on gastric secretion from the vagally innervated stomach of the dog. The most likely inhibitory mechanism seems to be represented by a decrease of the vagal activity.

Animals↗
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Gastroprotective effects of pantoprazole against experimental mucosal damage.

The present study investigated the gastroprotective effects of the proton pump inhibitor pantoprazole on gastric mucosal damage induced by ethanol-HCl in rats. Omeprazole was used as reference drug. The morphometric analysis of gastric histological sections revealed that pantoprazole and omeprazole dose-dependently prevented the necrotic mucosal injury evoked by ethanol-HCl (ED50 = 14.1 and 21.6 micromol/kg, respectively). These effects were associated with a marked increment of Alcian blue recovery from gastric bound mucus (ED50 = 18.8 and 29.3 micromol/kg, respectively). In addition, both pantoprazole and omeprazole inhibited gastric acid secretion in pylorus-ligated rats (ED50 = 1.5 and 3.3 micromol/kg, respectively). Further experiments indicated that the protective effects of pantoprazole were not modified by L-365,260 (a gastrin receptor antagonist), suramin (a drug able to interfere with endogenous growth factors), N(G)-nitro-L-arginine (an inhibitor of nitric oxide synthase) or systemic ablation of capsaicin-sensitive sensory nerves, whereas they were partly blocked by indomethacin (an inhibitor of prostaglandin synthesis) and fully prevented by N-ethylmaleimide (a potent blocker of sulfhydryl compounds). The present data provide histomorphometric evidence that: 1) pantoprazole is endowed with gastroprotective properties and is more active than omeprazole in preventing the necrotic mucosal damage induced by ethanol-HCl; 2) according to the rank order of ED50 values, the protective effects of both drugs appear to depend mainly on the enhancement of the gastric mucosal barrier rather than on the inhibition of acid secretion; 3) an increased production of prostaglandins, as well as an increased availability of sulfhydryl radicals at the level of the gastric mucosa may account for the gastroprotective effects of pantoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMedDate not supplied

Suramin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in metastatic colorectal cancer patients resistant to 5-FU+LV-based chemotherapy.

AIMS AND BACKGROUND: Suramin has been shown to be of interest as a potential new anticancer agent because of its capacity to inhibit the binding of several growth factors to their receptors and to inhibit the growth of cancer cells in vitro. Since multi-autocrine loops involving growth factors which are antagonized by suramin have been demonstrated in colorectal cancer, we previously evaluated the activity of suramin in patients with advanced colorectal cancer. Interestingly, in this study three patients who had received 5-FU+LV after suramin, although heavily pretreated with fluoropyrimidines, obtained an objective response. This observation was intriguing as it might have been that suramin had changed the biology of the tumor, making it sensitive to 5-FU+LV. We therefore conducted the present study to investigate the possibility that suramin might overcome the resistance to 5-FU+LV. METHODS AND STUDY DESIGN: Only colorectal cancer patients with metastatic and progressive disease during 5-FU+LV-based chemotherapy were eligible for this study. Suramin was administered for eight weeks at doses determined by means of a computer-assisted dosing algorithm that used Bayesian pharmacokinetics to maintain suramin plasma concentrations of 200-250 microg/ml. 5-FU was administered weekly at a dosis of 450 mg/m2 halfway through a two-hour infusion of I-LV 250 mg/m2 starting one week after the initiation of suramin for a maximum of 26 weeks. RESULTS: Treatment was relatively well tolerated, but no objective responses were observed after the accrual of 13 patients in the first stage of the trial. Consequently, the trial was interrupted according to the initial two-stage sampling design. CONCLUSIONS: The present study does not support the hypothesis that suramin might overcome resistance to 5-FU+LV and its use in colorectal cancer is not recommended.

Aged↗
PubMedDate not supplied

Peripheral cholecystokinin A and cholecystokinin B receptors mediate stimulation of gastric pepsinogen and acid secretion following intracerebroventricular injection of cholecystokinin-8-sulphate.

BACKGROUND: Peptides of cholecystokinin family regulate various physiological actions by acting at level of central nervous system. AIMS: To: 1) investigate possible influence of central cholecystokinin pathways on gastric pepsinogen and acid secretions; 2) characterize pharmacological profile and location of cholecystokinin receptor subtypes involved in gastric effects of centrally applied cholecystokinin-8-sulphate (cholecystokinin-8S). METHODS: Urethane-anaesthetized rats were subjected to continuous perfusion of gastric lumen. Pepsin levels in perfusate were determined by enzymatic assay based on spectrophotometric measurement of products generated by peptic digestion of bovine haemoglobin. Acidity was measured by automatic potentiometric titration of hydrogen ions. RESULTS: Following intracerebroventricular injection, cholecystokinin-8S increased both pepsinogen and acid output. In addition, intravenous cholecystokinin-8S stimulated peptic and acid secretions more promptly and at lower doses than after central injection. Stimulant effects of centrally applied cholecystokinin-8S were not affected by intracerebroventricular injection of devazepide (cholecystokinin A receptor antagonist) or L-365,260 (cholecystokinin B receptor antagonist) or by bilateral vagotomy. However, intravenous devazepide partly antagonized pepsigogue action of intracerebroventricular cholecystokinin-8S without affecting its acid hypersecretory effect, whereas after intravenous injection of L-365,260 peptic hypersecretion evoked by intracerebroventricular cholecystokinin-8S was partially prevented and acid response was completely blocked. Similar effects were exerted by intravenous devazepide and L-365,260 against intravenous cholecystokinin-8S. A complete blockade of pepsigogue effects induced by intracerebroventricular or intravenous cholecystokinin-8S was obtained after combined intravenous treatment with devazepide plus L-365,260. Gastric hypersecretory effects of intravenous cholecystokinin-8S were not modified by bilateral vagotomy. CONCLUSIONS: Increase in pepsinogen output evoked by centrally applied cholecystokinin-8S does not depend on interaction with central nervous sites. Following central or parenteral injection of cholecystokinin-8S, increase in peptic secretion would result from activation of both peripheral cholecystokinin A and B receptors presumably located at the level of gastric mucosa.

Analysis of Variance↗