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D Foschi

Publications and source records attributed to D Foschi.

54 records · Page 3Linked to original sources

Cytoprotection by PGE2, pirenzepine or vagotomy: a transmission and scanning electron microscopic study in rats.

We have studied the effects of PGE2, the anticholinergic pirenzepine and vagotomy on the rat gastric mucosa after challenge with ASA+0.15N HCl or absolute ethanol. The damage was evaluated by quantitative macroscopic examination, light and electron (transmission and scanning examinations) microscopy. We found both macroscopically and microscopically that pirenzepine and PGE2 were effective against ASA+0.15N HCl, but under microscopic examination they were seen to be uneffective 1 hr after absolute ethanol. Vagotomy showed some protection against ASA+0.15N HCl but was totally uneffective against absolute ethanol. The results stress the differences between ASA+0.15N HCl and absolute ethanol damage and show that "cytoprotection" is possible when the mucosa is challenged with noxious agents that do not act by hyperosmolar effects.

Animals↗

Adaptive cytoprotection: an endoscopic study in man.

We studied the protective effect of the mild irritant 20% ethanol against the damage caused by the strong irritant 40% ethanol to the duodenal mucosa of 10 healthy volunteers. At time 0, placebo (1% ethanol) or 20% ethanol (6 ml) was sprayed directly onto the duodenal wall through an endoscope. After 15 min 40% ethanol (50 ml) was given; damage was assessed by endoscopic examination 30 min after ethanol. The damage was scored arbitrarily: score 0, no damage; 1, duodenal hyperemia; 2, one hemorrhagic lesion; 3, two to five hemorrhagic lesions; 4, five hemorrhagic lesions. In separate experiments, the effect of acetylsalicylic acid (20 mg/kg iv) on adaptive cytoprotection was evaluated. It was found that 1) 20% ethanol does not damage the duodenal mucosa, whereas 40% ethanol does; 2) duodenal hyperemia and hemorrhagic lesions caused by 40% ethanol can be prevented by the previous administration of 20% ethanol; and 3) acetylsalicylic acid does not damage the duodenal mucosa but abolishes the protective effect of 20% ethanol. "Adaptive cytoprotection" is a physiological phenomenon in humans too and further supports the probable defensive role of endogenous prostaglandins in the gastrointestinal tract.

Adolescent↗

Indomethacin-induced intestinal ulcers in rats: effects of salicylazosulfapyridine and dexamethasone.

Characteristics of inflammatory bowel diseases have been hypothesized to resemble those of the syndrome of intestinal ulceration induced in the rat by non-steroidal anti-inflammatory compounds. However, no systematic studies have been undertaken to examine this possibility. Therefore, we have studied the influence of some pharmacological agents, such as steroids and salicylazosulfapyridine (SAS), which are clinically useful in the treatment of inflammatory bowel diseases, and to review published data on other pharmacological approaches commonly used for the therapy of inflammatory bowel diseases that have been shown to counteract indomethacin-induced intestinal toxicity. Orally administered SAS 100 to 800 mg/kg or dexamethasone 0.05 to 0.1 mg/kg exerted dose-related, anti-ulcer activity, with ED50 values and 95% confidence limits of 145 (95-222) mg/kg SAS and 0.184 (0.152-0.224) mg/kg dexamethasone. Other treatments, including cholestyramine, low-residue diets and antibiotics have also been reported to ameliorate clinical and experimental intestinal diseases. The clinical significance of present findings has been discussed.

Animals↗

Comparison of the gastric cytoprotective properties of atropine, ranitidine and PGE2 in rats.

In view of the controversy as to whether antisecretory agents such as H2 antagonists and antimuscarinics might be cytoprotective like the PGs, the oral activity of atropine, ranitidine and PGE2 against absolute ethanol-induced lesions was evaluated in rats. The results showed that atropine and PGE2, but not ranitidine, were effective in preventing absolute ethanol-induced gastric damage. The effects were related to the doses of the ulcerogenic agent and of the cytoprotective compound. The anti-ulcer activity of atropine is considered to be an expression of cytoprotection, since the pathogenesis of ethanol-induced gastric damage was independent of gastric pH and atropine, like PGE2, does not affect basal acid secretion at a fully cytoprotective dose. Some studies were undertaken to elucidate the mechanism of gastric cytoprotection by atropine. The possibility that the anti-muscarinic agent might work as a mild irritant was ruled out since, like PGE2, the agent was still effective in PG-deficient rats. The evidence that neostigmine markedly aggravated gastric damage caused by low doses of absolute ethanol and that atropine completely prevented this damage postulates mechanisms involving specific muscarinic receptor interactions.

Animals↗

A new technique for preparing continent gastric fistulas in dogs.

A new technique is described for making continent gastric fistulas in dogs. It is characterized by an antireflux flap of the gastric wall. It does not require a large laparotomy incision or gastric sutures, is simple, and takes only 30 minutes. Gastric secretion tests have demonstrated that this technique is followed by stable reproducible secretion.

Animals↗

The effects of 9-hydroxy-19,20-bis-norprostanoic acid on mucus, acid and gastrin secretion in duodenal ulcer patients.

The effects of 9-hydroxy-19,20-bis norprostanoic acid (rosaprostol, IBI), a new prostaglandin analogue, on gastric secretion and gastrin release were studied in 15 patients with duodenal ulcer. In acute experiments, rosaprostol lowered pentagastrin-stimulated acid secretion by 27-36%, whereas after chronic administration there were no changes in acid secretion or gastrin release (fasting and oxo-stimulated) but N-acetylneuraminic acid (NANA)-glycoproteins increased significantly. Our results indicate that the antisecretory and mucopoietic activities of 9-hydroxy-19,20-bis-norprostanoic acid are the basis of its healing effect in duodenal ulcer patients.

Adolescent↗

Further evidences on gastric cytoprotection exerted by pirenzepine.

Pirenzepine (P) exerts cytoprotective action through a mechanism so far poorly understood. The aim of the present work was to evaluate the protective effect of P and by comparison PGE2, in different cytoprotective models: NaOH 0.2 N; antral ulcer induced by indomethacin; and in an "in vivo" model using ethanol (50% 1ml/rat p.o.) as mucosal barrier damaging agent. In this last group of experiments gastric mucosal potential difference (DP), Na+ concentrations and pH were measured. These parameters provided a clear measure of the mucosal barrier recovery from damaging agents. P., like PGs, significantly protect mucosa against NaOH 0.2 N induced ulcers with an ED50 = 21.94 mg/kg os, a similar activity was found for the antral ulcers induced by indomethacin (ED50 22.06 mg/kg os). Moreover P. significantly antagonized the PD reduction induced by ethanol in rat. PGE2 was strikingly active in this model. P. and PGE2 significantly decreased also Na+ ion concentration altered by ethanol. Although this paper shows a positive effect of P on the gastric mucosal barrier, further studies are necessary to clarify the mechanism of gastric cytoprotection of P.

Animals↗

Pharmacokinetics of cimetidine in patients with unresponsive duodenal ulcer.

The pharmacokinetics of cimetidine after an oral dose of 400 mg were measured in 18 patients with duodenal ulcer, 9 refractory and 9 responders. The peak plasma concentration of cimetidine (2.13 +/- 0.17 micrograms/ml vs 1.43 +/- 0.04 micrograms/ml), the area under the plasma concentration curve (A.U.C.) between 0 to 8 hours after cimetidine (8.49 +/- 0.29 micrograms/ml/h vs 5.83 +/- 0.25 micrograms/ml/h), and the time span in which cimetidine was above 0.5 micrograms/ml (I.C.50) (401 +/- 8.86 min vs 296 +/- 20 min) were all found to be greater in responding patients than in non-responders to the therapy. No differences were detectable between the two groups in urinary excretion, T 1/2 of cimetidine or percentage inhibition (1%) of maximal pentagastrin-stimulated acid output (MAO). The results indicate that clinical healing of duodenal ulcer after cimetidine is related principally to the drug's pharmacokinetics, i.e. to its absorption from the small bowel, and that some other therapeutic approaches might be tried before surgery in cases of duodenal ulcer refractory to cimetidine.

Adult↗

Cytoprotection by PGE2, atropine, pirenzepine and vagotomy in rats.

Gastric cytoprotective effects of vagotomy, PGE2 and antimuscarinic compounds (pirenzepine, atropine) were studied in the rat. Both pharmacological and surgical treatment prevented the gastric damage induced by intragastric administration of acetylsalicylic acid plus hydrochloric acid. The mechanisms of action are discussed.

Animals↗

The colonization of Streptococcus faecium in human intestinal tract after oral administration.

The colonizing ability of Streptococcus faecium strain SF 68 at different levels of the gastrointestinal tract was assessed in ten patients. They were orally treated with a preparation containing the bacteria in lyophilized form for three days. During an abdominal surgical operation a sample of bacterial content of jejunum, ileum and colon was taken and cultured. The Streptococcus faecium was detected in all treated patients in a quite high concentration compared to the counts of both aerobic and anaerobic germs. These data confirms the rapid growth of SF 68 after oral administration in the gastrointestinal human tract.

Humans↗

Effects of intranasal neostigmine on oesophageal motility in man.

The effects of intranasally administered neostigmine on oesophageal peristalsis and lower oesophageal sphincter tone were investigated in 21 healthy volunteers. After 30 min of basal recording of oesophageal tracings, neostigmine (3 or 5.4 mg) or the inert vehicle were given. The oesophageal recording was continued for 45-60 min after administration. Neostigmine increased the amplitude and duration of the peristaltic waves without significantly affecting conduction. Lower oesophageal sphincter tone was also increased but post-swallowing relaxation was normal. At the highest dose, the effects of neostigmine lasted 45 min or more. There were no side effects and the heart rate was only slightly slowed. The results suggest that intranasal administration of neostigmine might be clinically useful for stimulation of upper gastrointestinal tract peristalsis.

Administration, Intranasal↗

New cyclosporine microemulsion randomized, cross-over bioequivalence steady-state study in renal transplanted patients.

A new microemulsion formulation of cyclosporine was compared with the marketed formulation in 18 stable renal transplanted patients. Aim of the study was not only to determine the bioequivalence between the two pharmaceutical preparations, but also to ascertain whether tested drug could maintain stable blood concentrations of cyclosporine. Renal transplanted patients under cyclosporine treatment from at least 12 months at a well individualized dosage (resulting in 90-200 ng/mL of blood level drug) have been selected. Patients received the same preceding dose of cyclosporine through both the two preparations according to a cross-over, randomized schedule during 4 weeks in two equally divided daily administrations. Serial blood samples were obtained over a 24-hour period at steady-state of each formulation. Cyclosporine concentrations were determined by a specific immunoassay method (FPIA) n whole blood taken in the last day of each cycle of treatment. Statistical comparisons of cyclosporine levels (using pharmacokinetic parameters) were cross-performed between formulations and days of blood test. Tested drug resulted bioequivalent with the reference marketed formulation. Furthermore, the study showed that tested drug maintained satisfactory stable blood concentrations of cyclosporine.

Adult↗

[Medical therapy of peptic ulcer: problems and prospects].

In the last few years, several drugs have been proposed for the healing of peptic ulcers H2 receptor antagonists are probably the reference-drugs for their efficacy and safety. Acute treatment of peptic ulcer with cimetidine, ranitidine or famotidine gives a high healing rate: from 60% to 90%, depending on the location of the ulcer and the drug used. However, relapse after short-term treatment still remains frequent, and prophylaxis of recurrence must be decided. Long-term treatment with antisecretory drugs could be dangerous for changes of the gastric system, with nitrites and nitro-compounds occurrence, and for the risk of frequent relapses. Therefore, the role of mucus-barrier drugs and surgery must be reconsidered.

Chemical Phenomena↗

Pouch ileitis in excluded reservoir: an unusual complication of restorative proctocolectomy for ulcerative colitis.

One case of pouch ileitis after restorative proctocolectomy for ulcerative colitis is described. Diagnosis was made by endoscopy, histology and electron microscopy. The most prominent feature was intense inflammation of the mucosa and submucosa, with atrophy of the villi, and colonic metaplasia, occurring before closure of the loop ileostomy. The patient improved after a course of metronidazole therapy, but ileostomy closure was postponed. It appears that the ileum mucosa of patients with ulcerative colitis is highly prone to the development of inflammation and careful, regular follow-up is recommended.

Adult↗

[Potential and limitations of conservative surgery in the treatment of gastric stump cancer].

In the Italian population the risk of gastric stump cancer after surgery for peptic ulcer is increased after 20-30 years. Bearing in mind that further surgery has little curative chances, we examined the series seen at the Institute of General Surgery of the University of Milan (1983-1992) to investigate whether or not patients followed-up endoscopically have a better chance of cure after surgery. Although only 10 patients were available for evaluation, it was evident that patients found at endoscopic screening in stage 0 and I (UICC classification) had a good survival after surgery. Our results support the need of strict endoscopic follow-up of resected patients 20 or more years after surgery and the need of further investigations to establish whether or not resection is useful and safe for early lesions.

Adult↗