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Biomedical subjects

C G Fenn

Publications and source records attributed to C G Fenn.

7 recordsLinked to original sources
PubMed1995

Effect of longterm misoprostol coadministration with non-steroidal anti-inflammatory drugs: a histological study.

Prostaglandins are widely used in the prevention and healing of non-steroidal anti-inflammatory drug (NSAID) induced gastric and duodenal ulcers, but their longterm effect on the human gastric mucosa is unknown. This study assessed the effect of coadministration of prostaglandins with NSAIDs on the histology of the gastroduodenal mucosa. Histological appearances (using the Sydney system) of gastric biopsy specimens from 180 patients receiving longterm NSAID treatment of whom 90 had been receiving misoprostol (400-800 micrograms/day) for one to two years were studied. Both groups of patients were comparable with regard to clinical and demographic details. There was no significant difference (p > 0.1) in the prevalence of chronic gastritis (total, corpus or antrum only) between patients receiving (36 of 90 (40%)) or not receiving misoprostol (35 of 90 (39%)). Chronic gastritis was equally associated with the presence of Helicobacter pylori, 86% and 73% (p > 0.1), respectively, in the two groups. Significantly fewer patients receiving misoprostol had reactive gastritis than those receiving only NSAIDs (8 (9%) versus 27 (30%), p < 0.01). Reactive gastritis was not associated with H pylori. Thirty nine (43%) of the misoprostol treated patients had normal histology compared with 16 (18%) receiving only NSAIDs (p < 0.01). These results show two different patterns of gastric damage in patients receiving NSAIDs, namely chronic and reactive gastritis. Misoprostol treatment was associated with a significantly reduced prevalence of reactive gastritis and it is suggested that this, along with its antisecretory action, may explain the reduced prevalence of gastroduodenal lesions when coadministered with NSAIDs.

Adult↗
PubMed1989

Misoprostol reduces indomethacin-induced changes in human small intestinal permeability.

This study examined whether indomethacin-induced increases in small intestinal permeability in man are prevented by concomitant administration of a prostaglandin analog (misoprostol). Twelve male volunteers were tested as baseline, following misoprostol alone (200 micrograms, at -16, -12, -8.5, -4, -1.5, and +4 hr); following indomethacin alone (75 mg, at -8; 50 mg, -1 hr); and following coadministration of misoprostol and indomethacin as specified above. A 100-ml test solution containing 3-O-methyl glucose (0.2 g), D-xylose (0.5 g), L-rhamnose (1.0 g), and [51Cr]EDTA (100 microCi) was ingested at 8 AM, and a 5-hr collection made for marker analysis to assess active and passive carrier-mediated transport and trans- and intercellular permeation, respectively. Indomethacin increased the permeation of [51Cr]EDTA selectively, and this increase was significantly reduced by the coadministration of misoprostol. These changes were mirrored by changes in [51Cr]EDTA-L-rhamnose urine excretion ratios, which indicates that paracellular permeability was specifically altered. This study supports the suggestion that NSAIDs alter intestinal permeability by a mechanism involving reduced prostaglandin synthesis and indicates that coadministration of misoprostol with NSAIDs may reduce the frequency and severity of NSAID-induced small intestinal inflammation.

3-O-Methylglucose↗
PubMed1984

Interactions between ethanol and dietary fat in determining human platelet function.

Platelet aggregation to collagen and ADP in vitro was assessed in the plasma of healthy human volunteers both before and after drinking 700 ml of white wine. This had no effect on platelet aggregation when compared with samples from the same individuals taken on a separate occasion without alcohol consumption. However, when alcohol was taken with a meal high in saturated fat, a significant inhibitory effect on platelet aggregation was observed when compared to the effect of the meal alone. There was no such interaction when the meal associated with alcohol ingestion contained mainly unsaturated fats. The fatty acid composition of plasma and platelet membranes from these volunteers showed a significantly increased proportion of saturated fats after the saturated fat meal. The concomitant ingestion of ethanol did not prevent this change. The concentration of alcohol in plasma achieved (c. 25 mM) may directly inhibit platelet aggregation when the platelet membrane content of saturated fats is high.

Adenosine Diphosphate↗
PubMed1983

The human blood platelet as a model for studying interactions of ethanol with membrane lipids.

The effect of ethanol on human blood platelet aggregation is generally inhibitory, but aggregation caused by arachidonic acid is either unaffected or potentiated by ethanol. Of the other aggregatory agents tested, the calcium ionophore A23187, collagen, and thrombin were most inhibited by ethanol. These results suggest that in the case of collagen and ionophore A23187 ethanol may act to inhibit aggregation at some point between the rise in cytosolic calcium and the cleavage of membrane phospholipids associated with the platelet release reaction. A similar spectrum of inhibition was produced by the incorporation of unsaturated fats into the platelet or by reduction of divalent cations by addition of EDTA to the external medium. Platelets in which unsaturated fats were incorporated were less susceptible to inhibition by ethanol than those into which saturated fats had been incorporated.

Blood Platelets↗
PubMed1982

Inhibition of platelet aggregation by ethanol in vitro shows specificity for aggregating agent used and is influenced by platelet lipid composition.

Ethanol at physiologically tolerable concentrations inhibited platelet aggregation in vitro in a relatively specific way, which may be influenced by platelet membrane lipid composition. Aggregation to collagen, calcium ionophore A23187 and thrombin (low doses) were often markedly inhibited by ethanol, adrenaline and ADP responses were little affected, and aggregation to exogenous arachidonic acid was actually potentiated by ethanol. Aggregation to collagen, thrombin and A23187 was inhibited more by ethanol in platelets enriched with saturated fatty acids than in those enriched with unsaturated fats. Platelets enriched with cholesterol showed increased sensitivity to ADP, arachidonate and adrenaline but this increase in cholesterol content did not appear to influence the inhibition by ethanol of platelet responses. The results suggest that ethanol may inhibit aggregation by an effect on membrane fluidity and/or calcium mobilization resulting in decreased activity of a membrane-bound phospholipase.

Adenosine Diphosphate↗
PubMed1982

Effects of ethanol administration on platelet function in the rat.

When ethanol is administered to rats chronically by inhalation for 5-7 days to produce a final ethanol concentration in plasma of about 50 mM platelet aggregation in vitro to collagen is markedly inhibited. Platelet aggregation to ADP is relatively unaffected and there is no evidence of thrombocytopenia or morphological change in platelets on scanning and transmission electron microscopy. The changed sensitivity to collagen is not simply due to the presence of ethanol in plasma during the in vitro tests because in vitro addition of a similar concentration of ethanol produces a much smaller inhibition of platelet aggregation to collagen in platelet-rich plasma from control animals. The acute or subacute administration of ethanol either by injection (3 g/kg-1 intraperitoneally) or by inhalation (4-6 h) produced very variable results, platelets from some animals being inhibited with respect to collagen as much as those from animals chronically exposed to ethanol, whereas other showed no inhibition other than that attributable to the presence of ethanol in plasma. When ethanol was administered chronically by inhalation for 30 days, thrombocytopenia was apparent and platelets from these animals were unresponsive to all aggregating agents tested. It is concluded that even relatively short periods of ethanol intake may lead to significant inhibition of platelet function, specifically aggregation to collagen. This may be of relevance to the suggested protective effect of ethanol intake in cardiovascular disease.

Adenosine Diphosphate↗