Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021933 (intussusception)
 3,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of intussusception (IN) remains largely obscure. In lipopolysaccharide (LPS)-induced IN, an experimental model in mice, IN is considered to be the consequence of altered intestinal motility as a result of increased nitric oxide (NO) along various inflammatory mediators. These could be decreased via cyclooxygenase (COX) inhibition by indomethacin. N-omega-nitro- L-arginine methyl ester ( L-NAME) inhibits nitric oxide synthase (NOS) and NO production. Indomethacin is known to prevent IN; however, the reason is unknown. In this study we aimed to determine the role of NO, the effects of inhibition of its production by L-NAME and indomethacin, and whether preventive effects of indomethacin on LPS-induced IN were related to NO inhibition. A total of 113 mice were divided into seven groups. In the control group ( n=6), no procedure was done. In the sham group ( n=6), 1 ml saline was given; in the indomethacin group ( n=6), 10 mg/kg of indomethacin was given; and in the LPS group ( n=30), 12 mg/kg of LPS was administered intraperitoneally (IP). In the LPS+indomethacin group ( n=32), 10 mg/kg of indomethacin was administered IP simultaneously with 12 mg/kg of LPS. In the L-NAME group ( n=6), 20 mg/kg of L-NAME was administered subcutaneously. In LPS+L-NAME group ( n=27), 20 mg/kg of L-NAME was administered subcutaneously with 12 mg/kg of LPS IP. All animals were laparotomized 6 h following injections. Existence of IN was noted and blood specimens were obtained. NO was quantified by measurements of nitrite and nitrate, obtaining a total of NO metabolites (NOx). The results were compared using the Mann-Whitney U-test and Spearman correlation test. A value of p<0.05 was considered significant. A total of 17 mice (one in control, 10 in LPS, four in LPS+indomethacin, and two in LPS+L-NAME groups) were excluded from the study because of death or insufficient blood collection. LPS (12 mg/kg, IP) induced IN at a rate of 30% ( n=6) in the LPS group. Mean NOx levels were statistically higher in the LPS group (186.67+/-20.06) compared with other groups ( p<0.05). Mean NOx levels were significantly higher in the group of mice with IN than in those without in the LPS group of this study (295.46+/-16.42, 140.05+/-15.44, respectively, p<0.05). The mean NOx levels were statistically lower in the LPS+ L-NAME(23.94+/-3.39) group than the LPS+indomethacin (106.77+/-24.54) group, with no IN detected in neither of these two groups. Increased NOx levels induced by LPS correlated well with the occurrence of IN, and decreasing these levels via COX inhibition by indomethacin or NOS inhibition by L-NAME totally prevented IN from forming in this study. By these observations, it could be concluded that NO is probably involved in the pathophysiology of IN in this experimental model of LPS-induced IN.
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PMID:Role of nitric oxide and cyclooxygenase pathway in lipopolysaccharide-induced intussusception. 1533 71

Medical countermeasures provide a key role in the UK integrated approach to chemical defence and are aimed at preventing or mitigating the effects of exposure to nerve agents. It is UK policy that medical countermeasures will be licensed products. Demonstration of efficacy relies on extrapolation of animal-derived data to man which means that species selection is extremely important. For the foreseeable future it is likely that a combination of pretreatment and therapy will be required to provide protection against nerve agent poisoning. There is a longer-term aspiration to develop a post poisoning-therapy which would reduce the reliance on pretreatment, prevent or mitigate the effects of exposure to all nerve agents and decrease the requirement for three autoinjectors. Immediate therapy comprising physostigmine (0.2mg/kg), hyoscine hydrobromide (4mg/kg) and HI-6 (93.6mg/kg) protected all animals against the lethal effects of a supralethal dose of GD, when given 1min after nerve agent poisoning in the absence of any pretreatment. In contrast when hyoscine hydrobromide was replaced with hyoscine methyl nitrate most of the animals died within 24h, whereas when an equal mixture of hyoscine hydrobromide and hyoscine methyl nitrate was used all the animals survived. None of these animals had an intussusception. It would not be possible to deliver these doses of HI-6 to a human from a single autoinjector device. Recent studies have shown that a lower dose of HI-6 (7mg/kg) which can be delivered via an autoinjector, in combination with physostigmine and hyoscine hydrobromide provides good protection against the lethal effects of a supralethal dose of GD. A number of animals died between 6 and 24h and had an intussusception. The surviving animals did not begin to regain weight until 48h after poisoning. In contrast when a mixture of hyoscine hydrobromide and hyoscine methyl nitrate was used, one animal died within 15min, the other animals all survived, regained weight from 24h and did not have an intussusception. These studies will now be extended to include other agents and will be taken forward to studies in non-human primates where the incidence of intussusception will be closely monitored.
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PMID:Development of next generation medical countermeasures to nerve agent poisoning. 1697 8