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Biomedical subjects

D Foschi

Publications and source records attributed to D Foschi.

At least 37 records · Page 2Linked to original sources

Heparin prevents stasis-induced thrombosis through protection of the venous endothelial cells: an electron microscopic study in rabbits.

This study was performed to see whether or not protection of the endothelial cells contributes to the antithrombotic effects of heparin. New Zealand albino rabbits were subjected to jugular vein stasis by single caudal ligation for 2 h. Three treatments were given: saline (control group), heparin (0.2 mg/kg) 5 or 45 min before ligature of the vein. Groups of 6-8 animals were killed at 0, 5, 15, 30 and 120 min. The following parameters were determined: (1) involution and damage of the endothelial cells by scanning and transmission electron microscopy; (2) incidence and weight of thrombi in the lumens of the veins after 2 h stasis, and (3) effects of heparin on APTT and anti-Xa activity. In the control group, stasis caused a considerable involution of the endothelial cells in the first 30 min, followed by fibrin deposition and thrombus generation. Heparin strongly reduced the damage to the endothelial cells, with very evident protection of the cell membranes, and prevented thrombus generation: there were significant decreases in both incidence and weight of thrombi. These effects of heparin were evident both shortly after (maximal anticoagulant effect) and long after (no anticoagulant effect) pretreatment. We think that, under the experimental conditions we used, heparin prevented venous thrombosis at least partially by protection of the endothelial cells, through unknown mechanisms.

Animals↗

The effects of L-sulpiride on reflux oesophagitis.

Prokinetic drugs are commonly used for treatment of reflux oesophagitis. Although much data has been collected in clinical trials, their therapeutic effects are still uncertain. In this study the effects of L-sulpiride, if any, were examined when used to treat reflux oesophagitis in thirty patients. The patients were divided into two groups: a control group and a group given 25 mg t.i.v./day, p.o. of L-sulpiride for 30 days. They were treated as outpatients and had endoscopic, histological and ultrastructural examinations on the 30th and 60th days of treatment. It was found that the symptoms of patients with reflux oesophagitis were alleviated and the endoscopic and ultrastructural lesions of patients with minor oesophagitis were also decreased. In other patients, symptoms improved without resolution of the lesions. The authors conclude, therefore, that L-sulpiride would be appropriate treatment for Grade I cases.

Double-Blind Method↗

Hyaluronic acid prevents oxygen free-radical damage to granulation tissue: a study in rats.

Oxygen free-radicals are known to impair wound healing after ischaemia-reperfusion or polymorphonuclear cell stimulation. Furthermore, they reduce the breaking strength of all recent wounds and might be a cause of wound leakage. This study was performed to evaluate whether or not hyaluronic acid can reduce the risk of wound impairment caused by free-radicals, in rats with abdominal sepsis, polymorphonuclear cell stimulation or cytochrome C function derangement produced by xenobiotics. Male Sprague-Dawley rats with open wounds received phenazine methosulfate or zimosan, or had abdominal sepsis to induce oxygen free-radical generation. There were three groups of treatment: hyaluronic acid cream, hyaluronic acid ethyl ester gel, and placebo. The reduction in wound size was measured from the 1st to the 11th postoperative day; biopsies were taken for histological evaluation. Every other day, a gentle debridement was performed in all the groups of animals. We found that hyaluronic acid and its ethyl ester derivative significantly improved the wound healing of rats subjected to an increased generation of oxygen free-radicals. It remains to be established whether or not hyaluronic acid acts as a scavenger of free-radicals.

Animals↗

Prostaglandin-stimulated recovery of the human duodenal epithelium: effects of misoprostol on ethanol damage.

This study was designed to determine whether prostaglandins can stimulate the repair of human duodenal epithelium. Ten healthy volunteers were given 50 ml 40% ethanol through an endoscope onto the duodenal mucosa 1-7 cm from the pyloric sphincter; 3 min later, misoprostol (200 micrograms) or inert vehicle (5 ml) was given locally in the same way. One and 5 h later, endoscopy was repeated to evaluate the damage. The conditions of the mucosa were evaluated by endoscopy and by scanning and transmission electron microscopy in biopsies taken at time 0 and 3 min, 1 and 5 h after ethanol. The study was double-blind with a cross-over balanced design. Three minutes after ethanol administration, the duodenal mucosa showed hyperemia with hemorrhagic lesions. Under the electron microscope, the lesions were caused by vascular engorgement or red blood cell extravasation into the submucosa; the epithelium underlining lesions showed loss of superficial cells and damage to the upper layer of the mucosa. One hour after ethanol, there was a striking difference between the two treatment groups, with a substantial recovery of the duodenal epithelium in the misoprostol-treated volunteers. Although spontaneous recovery was evident in the control group, there was also a significant difference at 5 h. Our results suggest that prostaglandins are able to stimulate the recovery of the duodenal epithelium after acute damage.

Alprostadil↗

Effects of autonomic nervous system on gastric damage by ethanol in the rat.

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.

Adaptation, Physiological↗

The role of mast cells in wound healing.

Mast cells are known to participate in three phases of wound healing: the inflammatory reaction, angiogenesis and extracellular-matrix reabsorption. The inflammatory reaction is mediated by released histamine and arachidonic acid metabolites. Compound 48/80 and disodium-cromoglycate are both able to increase skin breaking strength shortly after wounding. Under light and electron microscopy we found that small, granule-poor, irregular mast cells (MLMC) accumulate in the wound. This suggests that the small MLMC (mucosal-like mast cells) migrate into the skin during wound healing, and that both CTMC (connective-tissue mast cells) and MLMC are involved in tissue repair. Moreover, there is some evidence that mast cells participate in angiogenesis, since heparin is able to stimulate endothelial-cell migration and proliferation in vitro, and protamine to inhibit these processes and also angiogenesis in vivo. When the effect of protamine on wound breaking strength was examined, we encountered a decrease which was not prevented by heparin administration. Further studies are needed to demonstrate that protamine is specifically involved in inhibiting heparin-mediated angiogenesis in wounded tissue. Finally, mast cells may play a role in the extracellular matrix remodelling, on the basis of in-vitro experiments (but there are still no in-vivo data).

Animals↗

The effects of oxygen free radicals on wound healing.

We have examined the effects of oxygen free radicals, generated by xenobiotics administration, ischaemia-reperfusion or sepsis, on the healing of skin or intestinal wounds in rats. We found that 5 days after operation there was a significant decrease in the wound breaking strength in rats treated with phenazine methosulfate, zymosan, ischaemia-reperfusion or retroperitoneal infection. These changes were specifically prevented by administration of superoxide-dismutase (SOD), aprotinin and (in some models) allopurinol. On the contrary, none of these measures was effective when a local trauma caused the decrease in breaking strength. Our results suggest that oxygen free radicals mediate the inhibition of wound healing following ischaemia-reperfusion and sepsis.

Allopurinol↗

Prevention of wound dehiscence in severely obese patients with jejuno-ileal by-pass: the role of hyaluronic acid.

There is a high incidence of wound dehiscence, ranging from 6.9% to 22%, after surgery for severe obesity. Different surgical techniques to minimize this drawback of the operation have been proposed, but none have seemed to be really effective. A different approach to this problem has been tried using topical treatment with hyaluronic acid through the drains of the laparotomy suture. Twenty patients subjected to jejuno-ileal by-pass for severe obesity were randomized into two treatment groups: hyaluronic acid (80 mg/daily) or placebo (saline), for 5 days, starting at the operation. Granulation tissue was withdrawn from the wound through polyvinyl catheters 1, 3 and 5 days after the operation. It was processed for light, scanning and transmission electron microscopy. Ten days after the operation, the wounds were examined for dehiscence. Hyaluronic acid treatment reduced the incidence and degree of dehiscence macroscopically, increased the maturation of granulation tissue during the first post-operation days and stimulated fibroblasts to synthesize procollagen shortly after the operation.

Adult↗

Prostaglandin cytoprotection in man: effectiveness of rosaprostol.

We studied the effect of a new prostaglandin analogue, 9-hydroxy-19,20-bis-norprostanoic acid (rosaprostol), on the duodenal mucosa of humans after administration of 40% ethanol. Eighteen healthy volunteers entered the study, which followed a blind cross-over design. At time 0 all the volunteers received rosaprostol or placebo; 5 minutes later, 40% ethanol (50 ml dose) was given. The mucosa was examined for lesions 3, 60 and 180 min later under endoscopy, light and scanning microscopy. It was found that: (i) 40% ethanol damaged the duodenum, with blood extravasation, inflammation and necrosis of the mucosa, (ii) rosaprostol significantly protected the mucosa 3 min after 40% ethanol, and (iii) the damage became worse after 3 h when placebo was given, whereas it was reduced after 1 h when PG was administered. The results suggest that PGs not only protect the mucosa against ethanol damage, but also stimulate its recovery.

Adolescent↗

Hyperalimentation of jaundiced patients on percutaneous transhepatic biliary drainage.

Although percutaneous transhepatic biliary drainage (PTBD) restores hepatic and renal function in patients with obstructive jaundice, it is not certain whether it reduces the rate of complications and death after biliopancreatic surgery. We studied the possibility that the operative risks of jaundiced patients are related to malnutrition and the usefulness of hyperalimentation with PTBD to reduce the incidence of complications. Sixty-four patients with obstructive jaundice and serum bilirubin greater than 200 mumol/l were randomized into two treatment groups (n = 32) with PTBD or PTBD + hyperalimentation. Four patients were withdrawn from the latter group, two for metastatic cancer and two for complications of PTBD. Before starting hyperalimentation, the incidence of malnutrition was assessed by biochemical, immunological and anthropometric tests: malnutrition was found in 70 per cent of the patients. All the patients had good recovery of hepatic function but patients treated with PTBD alone still had high mortality (12.5 per cent) and morbidity (46.8 per cent) after biliopancreatic surgery. When hyperalimentation was provided to patients on PTBD for a period of 20 days before the operation, the incidence of complications fell to 17.8 per cent and mortality to 3.5 per cent. These results suggest that the combined use of PTBD and hyperalimentation, improving both hepatic function tests and the nutritional status of jaundiced patients, can reduce the rate of complications after biliary and pancreatic surgery.

Bile↗

Discontinuous oral absorption of cimetropium bromide, a new antispasmodic drug.

The pharmacokinetic profiles of cimetropium bromide, after either intravenous injection of 10 mg or oral ingestion of 200 mg, were determined in eight healthy volunteers. After intravenous administration, the plasma levels and urinary excretion indicated that the drug is distributed and eliminated at a rapid rate (terminal half-life, 50 +/- 8 min) and that urinary excretion is not the exclusive route of elimination (46 +/- 2%) of the administered dose). After oral administration, a low percentage of the drug is absorbed (1-4% of the administered dose), however, the amount is sufficient for therapeutic effect. The absorption is discontinuous, with two distinct phases, and ends abruptly during the second phase.

Administration, Oral↗

Protection of gastric mucosa in rats. Differences between vagotomy, atropine, and PGE2.

We have studied the protective effects of truncal vagotomy, atropine, and PGE2 against gastric mucosal injury produced by necrotizing agents (0.2 N NaOH, 0.6 N HCl, absolute ethanol), acetylsalicylic acid (ASA) and HCl, or serotonin (5HT). Vagotomy, atropine, and PGE2 prevent the effects of different noxious agents. Vagotomy is protective only against 5HT and against ASA + 0.15 N or 0.35 N HCl, whereas atropine and PGE2 are also protective against the necrotizing agents. The effectiveness of vagotomy against ASA + 0.35 N HCl does not depend on the inhibition of acid secretion and supports the hypothesis that removal of the vagal drive counteracts the effect of H+ back-diffusion.

Animals↗

Oxygen free radicals interact with indomethacin to cause gastrointestinal injury.

In the present study it was shown that, unlikely MK447, a known oxygen free radical compound, PGE2 is much less effective against indomethacin-induced G.I. ulcers than against ethanol damage. It seems likely that factors other than PG deficiency (such as oxygen free radicals), could be involved in the pathogenesis of NSAID-induced G.I. damage. Some compounds that can capture free radicals (aminopyrine, thiourea and its derivative, MK 447) or that inhibit the lipoxygenase pathway (MK 447, salicylazosulfapyridine, BW 755, benoxaprofen) are able to abolish indomethacin-induced G.I. damage. After irradiation with hydroxyl free radicals, indomethacin reacts with them to cause marked G.I. injury, even at a submaximal dose, one poorly ulcerogenic by itself. The above findings suggest that oxygen free radicals are one of the causal factors in the formation of NSAID-induced G.I. side effects. Some of the data in this paper were presented at Fermo, August 31, 1984 (Advanced course on 'oxygen and sulfur radicals in chemistry and medicine') and at the 9th Iuphar International Congress of Pharmacology in London, July 30, 1984.

Animals↗