Cytoprotection and healing: Two unequal brethren

The promotion of the concept of cytoprotection has fostered hopes that the use of co-prescribed mucosal protective agents would revolutionize the prevention of NSAID-induced ulcers and supply the basis for novel ulcer therapy. Prostaglandins do not, however, accelerate ulcer healing when applied at doses that exert an unequivocal cytoprotective activity. Attempts have therefore been made in recent years to create new less-toxic NSAIDs, such as combined lipoxygenase/cyclo-oxygenase inhibitors, NSAIDs coupled to an NO donor and so-called COX-2 inhibitors. All these preparations do in fact exert a diminished gastrointestinal toxicity. There is however increasing evidence accumulating from studies performed in and outside our laboratories that in chromic ulcer models their increased gastrointestinal tolerance is not necessarily reflected by non-interference with ulcer healing. It is thus mandatory to distinguish between cytoprotective and healing properties of drugs interfering with the cyclo-oxygenase pathwa

Healing Potential of Picrorhiza kurroa (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration.

<p>Abstract</p> <p>Background</p> <p>The present study was undertaken to evaluate the potential of the rhizomes of the Indian medicinal plant, <it>Picrorhiza kurroa </it>in healing indomethacin-induced acute stomach ulceration in mice and examine its capacity to modulate oxidative stress and the levels of prostaglandin (PGE₂) and EGF during the process.</p> <p>Methods</p> <p>Male swiss albino mice, ulcerated with indomethacin (18 mg/kg, p. o., single dose) were treated up to 7 days with different doses of the methanol extract of <it>P. kurroa </it>rhizomes (designated as PK). The healing capacity of the most effective dose of PK (20 mg/kg, p. o. × 3 d) was compared with that of omeprazole (Omez) (3 mg/kg, p. o. × 3 d). The effects of the drug-treatment for one and three days on the biochemical parameters were assessed by comparing the results with that of untreated mice of the 1^stand 3^rdday of ulceration. The stomach tissues of the mice were used for the biochemical analysis.</p> <p>Results</p> <p>The macroscopic indices revealed maximum ulceration on the 3^rdday after indomethacin administration, which was effectively healed by PK. Under the optimized treatment regime, PK and Omez reduced the ulcer indices by 45.1% (<it>P </it>< 0.01), and 76.3% respectively (<it>P </it>< 0.001), compared to the untreated ulcerated mice.</p> <p>Compared to the ulcerated untreated mice, those treated with PK for 3 days showed decreased the levels of thiobarbituric acid reactive substances (TBARS) (32.7%, <it>P </it>< 0.05) and protein carbonyl (37.7%, <it>P </it>< 0.001), and increased mucin (42.2%, <it>P </it>< 0.01), mucosal PGE₂(21.4%, <it>P </it>< 0.05), and expressions of COX-1 and 2 (26.9% and 18.5%, <it>P </it>< 0.05), EGF (149.0%, <it>P </it>< 0.001) and VEGF (56.9%, <it>P </it>< 0.01). Omez reduced the TBARS (29.4%, <it>P </it>< 0.05), and protein carbonyl (38.9%, <it>P </it>< 0.001), and increased mucin (38.3%, <it>P </it>< 0.01), without altering the other parameters significantly.</p> <p>Conclusion</p> <p>PK (20 mg/kg, p. o. × 3 days) could effectively heal indomethacin-induced stomach ulceration in mice by reducing oxidative stress, and promoting mucin secretion, prostaglandin synthesis and augmenting expressions of cyclooxygenase enzymes and growth factors.</p

The Rotterdam Study: 2012 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods