Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intussusception is a major cause for intestinal obstruction in children. Its etiology is unclear, but it is often associated with some kind of infection. We have developed a model for intussusception in mice using intraperitoneal (IP) injection of lipopolysaccharide (LPS). The objective of this study was to identify the putative mediators that participate in this LPS-induced intussusception. LPS (12 mg/kg) was injected into adult mice (N = 52) and 6 hr later, 25% of the animals demonstrated intussusception in the small or large intestine. We next tested whether nitric oxide (NO) or various inflammatory mediators contributed to this effect: Indomethacin (10 mg/kg) injected with LPS (12 mg/kg) completely prevented the effect of LPS (N = 20). The tumor necrosis factor (TNF) blocker pentoxifylline (200 mg/kg) significantly reduced the incidence of intussusception to 6.6% (N = 30). The platelet-activating factor (PAF) antagonist BN52021 (10 and 20 mg/kg) reduced the incidence of intussusception to 13.3% in both doses (N = 15 for each dose). Addition of 2% arginine (NO precursor) to the drinking water 36 hr before the injection of LPS increased the incidence of intussusception to 30.7% (N = 32). In mice injected with the NO synthase inhibitor L-NAME (20 mg/kg) only 3.8% developed intussusception (N = 26). Our results indicate that the induction of intussusception by LPS proceeds via parallel pathways involving cytokines, prostaglandins, and NO. Our previous pathological study showed that LPS did not cause any changes that may act as a lead point for the intussusception, suggesting that LPS induced intussusception by altering gut motility. We therefore propose that these mediators combine to induce disturbed gut motility that results in the formation of intussusception.
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PMID:The contribution of inflammatory mediators and nitric oxide to lipopolysaccharide-induced intussusception in mice. 920 71

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

Unexpected reports of intussusception after vaccination with the live tetravalent rotavirus vaccine RotaShield resulted in voluntary withdrawal of the vaccine. Intussusception, a condition in which the intestine acutely invaginates upon itself, is the most common cause of intestinal obstruction in children. We report here the development of a mouse model to study rotavirus-induced intussusception. In this model, both homologous murine and heterologous simian rotavirus strains significantly enhanced the rate of lipopolysaccharide (LPS)-induced intussusception, and this enhancement was replication dependent, requiring rotavirus doses of greater than one 50% infectious dose. Rotavirus-induced intussusceptions did not have observable lymphoid lead points, despite the induction of intestinal lymphoid hyperplasia after rotavirus infection. Intussusceptions are also postulated to result from altered intestinal motility, but rotavirus infection had no effect on gastrointestinal transit. LPS-induced intussusception is associated with the induction of inflammatory mediators, and intussusception rates can be modified by inflammatory antagonists. We show that rotavirus infection significantly enhanced serum tumor necrosis factor alpha and gamma interferon cytokine levels after LPS treatment compared to uninfected mice. Together, these data suggest that rotavirus infection sensitized mice to the inflammatory effects of subsequent LPS treatment to enhance intussusception rates.
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PMID:Rotavirus infection enhances lipopolysaccharide-induced intussusception in a mouse model. 1700 39

Intussusception (IS), an invagination of a portion of the intestine into itself, has recently attracted considerable interest after the withdrawal of a rotavirus vaccine because of reports on increased risk of IS shortly after vaccination. The present study was designed to shed further light on the mechanism of IS formation and its prevention. Intussusception was induced in adult mice by intraperitoneal injection of lipopolysaccharide (LPS; 8 mg/kg) from salmonella typhimurium. The presence of IS was confirmed at laparotomy. The serum levels TNF-alpha were measured with ELISA. Six hours after LPS injection, 14.5% of the animals demonstrated IS. A total of 65 animals received rofecoxib (20 mg/kg), a selective COX2 inhibitor, 15-30 min before intraperitoneal injection of LPS, and only two (3%) in this group demonstrated IS 6 h later (P < 0.05 vs. control). We confirmed the well-known increase in serum TNF-alpha levels in response to LPS; however, this increase was not blocked by rofecoxib pretreatment. Notably, there was no correlation between the serum TNF-alpha levels and the development of IS. The results show that the occurrence of IS can be significantly decreased by pretreatment with a selective COX-2 inhibitor.
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PMID:Prevention of lipopolysaccharide-induced intussusception in mice by the COX2 inhibitor rofecoxib. 1798 32

Intussusception is one of the most common abdominal emergencies in children. The understanding of its aetiology and management has changed significantly over the last decades. Earlier, the hypertrophic Peyer's patches and polyps were considered responsible, but with the knowledge obtained from the lipopolysaccharide-induced animal model of intussusception, the rotavirus vaccination, the seasonality and the postnatal changes of the enteric nervous system it became clear that the intestinal motility plays a key role in the aetiology. The efficacy of non-operative management is continuously improving. The radiologists initially moved from the hydrostatic X-ray-controlled reduction towards the air enema (pneumatic reduction), however, nowadays, there is a shift back to hydrostatic procedures but under ultrasound guidance to reduce radiation exposure. In many institutions, intussusception is managed as day-case rather than as an inpatient case. The role of medications like glucagon and cyclo-oxygenase inhibitors used during reduction manoeuvres and prevention of recurrence is still controversial. Surgical management is shifting towards laparoscopy. The authors herein reviewed the current literature to present recent insights into understanding the pathogenesis and management updates. Orv Hetil. 2020; 161(32): 1331-1338.
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PMID:Modern understanding of intussusception and recent trends in management 3275 21