Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
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Cyclo-oxygenase (prostaglandin endoperoxide synthase) is the enzyme which metabolizes the conversion of arachidonic acid to prostaglandin. It exists in at least two isoforms: the constitutive (cyclo-oxygenase-1) and the inducible (cyclo-oxygenase-2) which is controlled by a number of factors, including cytokines and intracellular messengers. These enzymes are the therapeutic targets of non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen. ⋯ Although cyclo-oxygenase-1 seems to be expressed in physiological conditions and cyclo-oxygenase-2 in inflammatory conditions, it is not yet possible to identify all their different roles. Cyclo-oxygenase-2 may be expressed constitutively, whereas the generation of prostaglandin by cyclo-oxygenase-2 may replace that by cyclo-oxygenase-1 in some situations (or vice-versa). Both cyclo-oxygenase isoenzymes contribute to mucosal defence and the inhibition of the two isoforms contributes to the pathogenesis of non-steroidal anti-inflammatory drug-induced gastric damage.
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Non-alcoholic steatohepatitis is a chronic liver disease that is capable of progressing to end-stage liver disease, but generally has a benign course. Obesity, non-insulin-dependent diabetes mellitus and hyperlipidaemia are the most common associations of the disease. ⋯ Our study revealed marked hyperinsulinaemia and insulin resistance in patients with non-alcoholic steatohepatitis. Hyperinsulinaemia and insulin resistance may contribute to pathogenesis of nonalcoholic steatohepatitis.
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Comparative Study
Gastroprotective and ulcer healing effects of nitric oxide-releasing non-steroidal anti-inflammatory drugs.
New class of nitric oxide-releasing non-steroidal anti-inflammatory drugs was shown to inhibit cyclooxygenase and prostaglandin generation without causing mucosal damage but whether these agents are capable of affecting gastric mucosal damage induced by strong irritants and healing of chronic gastric ulcers remains to be studied. In this investigation, effects of nitric oxide-releasing aspirin and nitric oxide-releasing naproxen were compared with those of native agents on gastric lesions provoked by 100% ethanol and on healing of chronic acetic acid ulcers. ⋯ 1) Coupling of nitric oxide to aspirin or naproxen attenuates ethanol-induced damage, possibly due to an increase in gastric microcirculation mediated by excessive release and action of nitric oxide that probably compensates for PG deficiency induced by non-steroidal anti-inflammatory drugs; and 2) nitric oxide-non-steroidal anti-inflammatory drug, unlike classic non-steroidal anti-inflammatory drugs, does not affect intact gastric mucosa and fails to delay the healing of pre-existing ulcers.