Anti-inflammatory and antioxidant effects of the nanocomposite Fullerol decrease the severity of intestinal inflammation induced by gut ischemia and reperfusion.

Intestinal ischemia is a vascular emergency that arises when blood flow to the intestine is compromised. Reperfusion is necessary to restore intestinal function but might lead to local and systemic inflammatory responses and bacterial translocation, with consequent multiple organ dysfunction syndrome (MODS). During reperfusion occurs production of reactive oxygen species. These species contribute to intestinal injury through direct toxicity or activation of inflammatory pathways. Fullerol is a nanacomposite which has been shown to act as reactive oxygen species and reactive nitrogen species (RNS) scavengers. Thus, our aim was to evaluate whether Fullerol confer anti-inflammatory activity during intestinal ischemia and reperfusion (IIR). Intestinal ischemia was induced by total occlusion of the superior mesenteric artery. Groups were treated with vehicle or Fullerol 10 min before reperfusion. Mice were euthanized after 6 h of reperfusion, and small intestines were collected for evaluation of plasma extravasation, leukocyte influx, cytokine production and histological damage. Bacterial translocation to the peritoneal cavity and reactive oxygen and nitrogen species production by lamina propria cells were also evaluated. Our results showed that treatment with Fullerol inhibited bacterial translocation to the peritoneal cavity, delayed and decreased the lethality rates and diminished neutrophil influx and intestinal injury induced by IIR. Reduced severity of reperfusion injury in Fullerol-treated mice was associated with blunted reactive oxygen and nitrogen species production in leukocytes isolated from gut lamina propria and decreased production of pro-inflammatory mediators. Thus, the present study shows that Fullerol is a potential therapy to treat inflammatory bowel disorders associated with bacterial translocation, such as IIR.

Gut Microbiota Restricts NETosis in Acute Mesenteric Ischemia-Reperfusion Injury.

OBJECTIVE: Recruitment of neutrophils and formation of neutrophil extracellular traps (NETs) contribute to lethality in acute mesenteric infarction. To study the impact of the gut microbiota in acute mesenteric infarction, we used gnotobiotic mouse models to investigate whether gut commensals prime the reactivity of neutrophils towards formation of neutrophil extracellular traps (NETosis). Approach and Results: We applied a mesenteric ischemia-reperfusion (I/R) injury model to germ-free (GF) and colonized C57BL/6J mice. By intravital imaging, we quantified leukocyte adherence and NET formation in I/R-injured mesenteric venules. Colonization with gut microbiota or monocolonization with Escherichia coli augmented the adhesion of leukocytes, which was dependent on the TLR4 (Toll-like receptor-4)/TRIF (TIR-domain-containing adapter-inducing interferon-ß) pathway. Although neutrophil accumulation was decreased in I/R-injured venules of GF mice, NETosis following I/R injury was significantly enhanced compared with conventionally raised mice or mice colonized with the minimal microbial consortium altered Schaedler flora. Also ex vivo, neutrophils from GF and antibiotic-treated mice showed increased LPS (lipopolysaccharide)-induced NETosis. Enhanced TLR4 signaling in GF neutrophils was due to elevated TLR4 expression and augmented IRF3 (interferon regulatory factor-3) phosphorylation. Likewise, neutrophils from antibiotic-treated conventionally raised mice had increased NET formation before and after ischemia. Increased NETosis in I/R injury was abolished in conventionally raised mice deficient in the TLR adaptor TRIF. In support of the desensitizing influence of enteric LPS, treatment of GF mice with LPS via drinking water diminished LPS-induced NETosis in vitro and in the mesenteric I/R injury model. CONCLUSIONS: Collectively, our results identified that the gut microbiota suppresses NETing neutrophil hyperreactivity in mesenteric I/R injury, while ensuring immunovigilance by enhancing neutrophil recruitment.

Medical evacuation from abroad of critically ill patients: A case report and ethical issues.

RATIONALE: Patients repatriated from foreign hospitals are sources of extensively drug-resistant (XDR) bacteria outbreaks. Thus, an individual benefit potential for the patient opposes a collective ecological risk potential. These ethical issues have not been well studied. PATIENT CONCERNS: We report the case of a 74-year-old patient repatriated from Mauritius to the French island of Reunion who presented mesenteric infarction evolving over several days, and who suffered a cardiac arrest before transfer. DIAGNOSES: In Reunion Island, a CT-scan revealed a multisegmental enlarged parietal enlargement associated with free peritoneal effusion and a suboccluded aspect of the superior mesenteric artery. INTERVENTIONS: Surgical exploration showed a severe mesenteric infarction with peritonitis, and a resection of 120cm of the small intestine was conducted. This patient was infected with a vanA glycopeptide-resistant Enterococcus faecium and a carbapenem-resistant Klebsiella pneumoniae which produced carbapenemases NDM-1 and OXA-181, which required specific care and could have led to a local epidemic. OUTCOMES: The patient died after 9 days after being admitted to the ICU. LESSONS: Repatriation of critically ill patients from abroad should be considered according to ethical criteria, evaluating, if possible, the expected benefits, and ecological risks incurred. Limiting unnecessary transfers could be an effective measure to limit the spread of XDR bacteria.

Bacterial translocation and mortality on rat model of intestinal ischemia and obstruction.

PURPOSE:: To develop an experimental model of intestinal ischemia and obstruction followed by surgical resection of the damaged segment and reestablishment of intestinal transit, looking at bacterial translocation and survival. METHODS:: After anesthesia, Wistar rats was subject to laparotomy, intestinal ischemia and obstruction through an ileal ligature 1.5cm of ileum cecal valve; and the mesenteric vessels that irrigate upstream of the obstruction site to approximately 7 to 10 cm were ligated. Abdominal wall was closed. Three, six or twenty-four hours after, rats were subject to enterectomy followed by an end to end anastomosis. After 24h, mesenteric lymph nodes, liver, spleen and lung tissues were surgically removed. It was studied survival rate and bacterial translocation. GraphPadPrism statistical program was used. RESULTS:: Animals with intestinal ischemia and obstruction for 3 hours survived 24 hours after enterectomy; 6hx24h: survival was 70% at 24 hours; 24hx24h: survival was 70% and 40%, before and after enterectomy, respectively. Culture of tissues showed positivity on the 6hx24h and negativity on the 3hx24h. CONCLUSION:: The model that best approached the clinic was the one of 6x24h of ischemia and intestinal obstruction, in which it was observed bacterial translocation and low mortality rate.

Bacterial translocation and mortality on rat model of intestinal ischemia and obstruction

Abstract Purpose: To develop an experimental model of intestinal ischemia and obstruction followed by surgical resection of the damaged segment and reestablishment of intestinal transit, looking at bacterial translocation and survival. Methods: After anesthesia, Wistar rats was subject to laparotomy, intestinal ischemia and obstruction through an ileal ligature 1.5cm of ileum cecal valve; and the mesenteric vessels that irrigate upstream of the obstruction site to approximately 7 to 10 cm were ligated. Abdominal wall was closed. Three, six or twenty-four hours after, rats were subject to enterectomy followed by an end to end anastomosis. After 24h, mesenteric lymph nodes, liver, spleen and lung tissues were surgically removed. It was studied survival rate and bacterial translocation. GraphPadPrism statistical program was used. Results: Animals with intestinal ischemia and obstruction for 3 hours survived 24 hours after enterectomy; 6hx24h: survival was 70% at 24 hours; 24hx24h: survival was 70% and 40%, before and after enterectomy, respectively. Culture of tissues showed positivity on the 6hx24h and negativity on the 3hx24h. Conclusion: The model that best approached the clinic was the one of 6x24h of ischemia and intestinal obstruction, in which it was observed bacterial translocation and low mortality rate.

Explantation of infected aortic aneurysm and endograft with ascending aorta to mesenteric bypass for mesenteric ischemia.

A 65-year-old man presented with an infected perivisceral aortic aneurysm after previous treatment of an abdominal aortic aneurysm with an endograft. On presentation, he was septic and had occlusion of the celiac, superior mesenteric, inferior mesenteric, and bilateral renal arteries. He underwent a three-stage procedure: first, axillobifemoral bypass; then resection of the thoracoabdominal aorta; and finally bypass from the ascending aorta to the celiac and superior mesenteric arteries with a rifampin-soaked Gelsoft graft (Vascutek, Renfrewshire, Scotland). The abdominal pain resolved, and the patient remains symptom free 10 months postoperatively. This rare surgical revascularization technique offered a nontraditional solution to a difficult surgical issue.

Impaired intestinal mucosal barrier upon ischemia-reperfusion: "patching holes in the shield with a simple surgical method".

UNLABELLED: Mesenteric ischemia-reperfusion (IR) is associated with impairment of the gut barrier function and the initiation of a proinflammatory cascade with life-threatening results. Therefore methods directed to ameliorate IR injury are of great importance. We aimed at describing the effects of postconditioning (PC) on the alterations of the intestinal mucosal function and the inflammatory response upon mesenteric IR. METHODS: Male Wistar rats were gavaged with green fluorescent protein-expressing E. coli suspensions. Animals were randomized into three groups (n = 15), sham-operated, IR-, and PC-groups, and underwent 60 minutes of superior mesenteric artery occlusion, followed by 6 hours of reperfusion. Postconditioning was performed at the onset of reperfusion. Blood and tissue samples were taken at the end of reperfusion, for histological, bacteriological, and plasma examinations. RESULTS: The PC-group presented a more favorable claudin-2, claudin-3, claudin-4, and zonula occludens-1 membrane expression profile, and significantly lower rates of bacterial translocation to distant organs and plasma D-lactate levels compared to the IR-group. Histopathological lesions, plasma I-FABP, IL-6, and TNF- α levels were significantly lower in the PC-group compared to the IR-group. CONCLUSION: The use of postconditioning improved the integrity of the intestinal mucosal barrier upon mesenteric IR, and thus reduced the incidence of bacterial translocation and development of a systemic inflammatory response.

Infective endocarditis associated superior mesenteric artery pseudoaneurysm.

BACKGROUND: Since William Osler first described mycotic aneurysms in the setting of endocarditis in 1885, few pseudoaneurysms (PAs) of the superior mesenteric artery (SMA) have been reported in the literature. We report 2 cases of SMA PA related to infective endocarditis that were managed with open surgery. RESULTS: Here we report 2 cases of SMA PAs treated with different surgical techniques. A 59-year-old male with a history of intravenous drug use presented with abdominal pain and was found to have Streptococcus viridans endocarditis and an SMA PA. A laparotomy was performed, and proximal and distal control of the SMA PA was obtained. After ensuring that Doppler signals were still present in the distal mesentery and the entirety of the bowel was viable, the SMA was ligated proximal and distal to the PA. The patient recovered uneventfully. The second case is a 35-year-old female who presented with abdominal pain and was found to have Streptococcos gordonii endocarditis and an SMA PA for which the patient was initially observed. After several weeks, the patient's condition deteriorated and the patient underwent open ligation of the SMA, proximal and distal to the PA, with a bypass from the infrarenal abdominal aorta to a distal unnamed SMA branch and resection of 3 ft of ischemic small bowel. The patient continued to have recurrent bowel ischemia over the next several weeks and ultimately died. CONCLUSIONS: SMA PAs associated with infective endocarditis are rare, but carry a high risk of rupture and associated morbidity and mortality. Delay in surgical management may increase this risk.