Intracoronary application of nicorandil regulates the inflammatory response induced by percutaneous coronary intervention

Intracoronary application of nicorandil can effectively reduce the myocardial no‐reflow (MNR) after percutaneous coronary intervention (PCI). We sought to investigate the mechanisms of nicorandil in preventing MNR, besides that of dilating the coronary microvasculature. A total of 60 patients undergoing PCI were enrolled and randomly divided into a nicorandil group and a control group. Before PCI, 2 mg of nicorandil or an equal volume of normal saline was injected into the coronary artery. Blood samples were collected before, 24 hours and 1 week after PCI and inflammatory cytokines were tested. In the control group, the expression of pro‐inflammatory cytokines was significantly increased, while the anti‐inflammatory cytokines were decreased 24 hours after PCI. In contrast, these changes were reversed in the nicorandil group, indicating that nicorandil regulated the inflammatory response induced by PCI. Then, proteomic analysis was performed to further elucidate the potential mechanisms. A total of 53 differentially expressed proteins (DEPs) were found 24 hours after PCI in the control group, and the changes of these relevant genes were reversed in the nicorandil group. These DEPs were significantly enriched in the inflammatory pathways. In conclusion, the intracoronary application of nicorandil before PCI can regulate the inflammatory responses induced by PCI, which might be an important mechanism of nicorandil in preventing MNR.     

Gastric toxicity and mucosal ulceration induced by oxygen-derived reactive species: protection by melatonin

Uncontrolled hydrochloric acid secretion and ulceration of the stomach mucosa due to various factors are serious global problems. Although the mechanism of acid secretion from the parietal cell is now well understood, the processes involved in gastric ulceration are still not clear. Among various causes of gastric ulceration, lesions caused by stress, alcohol consumption, Helicobacter pylori infection and due to use of nonsteroidal antiinflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species, especially the hydroxyl radical. A number of excellent drugs have proven useful in controlling hyperacidity and ulceration but their long-term use is associated with disturbing side-effects. Hence, the search is still on to find a compound possessing antisecretory, antiulcer and antioxidant properties which will serve as a therapeutic agent to reduce gastric hyperacidity and ulcers. This article describes the role of reactive oxygen species in gastric ulceration, drugs controlling them with their merits and demerits and, the role of melatonin, a pineal secretory product, in protecting against gastric lesions. In experimental studies, melatonin has been shown to be effective in reducing mucosal breakdown and ulcer formation in a wide variety of situations. Additionally, the low toxicity of melatonin supports further investigation of this molecule as a gastroprotective agent. Finally, we include a commentary on how melatonin research with respect to gastric pathophysiology can move forward with a view of eventually using this indole as a therapeutic agent to control gastric ulceration in humans.     

Towards the mechanism of protection against indomethacin induced gastro-intestinal ulceration by naloxone

Activities of lysosomal hydrolases have been evaluated in relation to indomethacin and naloxone, using purified lysosomal fractions from rat intestinal mucosa. Indomethacin treatment significantly decreased (p less than 0.001) lysosomal enzyme activities in purified lysosomes, while an increase in the activities was observed in intestinal homogenates. However, indomethacin could not affect lysosomal system in animals pretreated with naloxone, thereby establishing that naloxone neutralises the effect of indomethacin.     

Prophylaxis by vitamin C in starvation induced rat stomach ulceration

Rats given L-ascorbic acid in their drinking water prior to and during starvation did not develop severe ulceration in the mucosal lining of their stomachs. Control rats which were either nontreated or given deactivated L-ascorbic acid developed severe stomach pathology on the starvation regimen.     

Acetic acid induced ulceration in rats is not affected by infection with Hymenolepis diminuta

Analysis of rodent models of inflammatory bowel disease, airways hyper-reactivity, diabetes, and multiple sclerosis has shown that infection with helminth parasites can significantly reduce the severity of the disease. Here, we assessed whether rats infected with the tapeworm Hymenolepis diminuta were protected from gastric ulceration induced by the serosal application of acetic acid. All rats gavaged with infective cysticercoids harbored adult worms when assessed 6 wk later, and acetic acid evoked the expected gastric ulceration. However, infection with H. diminuta did not affect the degree of gastric ulceration at either 3 or 7 days post-acetic acid application, as gauged by ulcer area or histopathology. While the data do not dismiss the possibility that infection with other helminths could be anti-ulcerogenic, they illustrate that 'helminth therapy' for inflammatory disease is likely to be both disease- and helminth-specific.