Taine Pechet

Intestinal ischemia-reperfusion injury is dependent on complement. This study examines the role of the alternative and classic pathways of complement and IgM in a murine model of intestinal ischemia-reperfusion. Wild-type animals, mice deficient in complement factor 4 (C4), C3, or Ig, or wild-type mice treated with soluble complement receptor 1 were subjected to 40 min of jejunal ischemia and 3 h of reperfusion. Compared with wild types, knockout and treated mice had significantly reduced intestinal injury, indicated by lowered permeability to radiolabeled albumin. When animals deficient in Ig were reconstituted with IgM, the degree of injury was restored to wild-type levels. Immunohistological staining of intestine for C3 and IgM showed colocalization in the mucosa of wild-type controls and minimal staining for both in the intestine of Ig-deficient and C4-deficient mice. We conclude that intestinal ischemia-reperfusion injury is dependent on the classic complement pathway and IgM.

BACKGROUND: The traditional treatment for clearly operable (CO) patients with stage I non-small cell lung cancer (NSCLC) is lobectomy, with wedge resection (WR) and stereotactic body radiation therapy (SBRT) serving as alternatives in marginally operable (MO) patients. Given an aging population with an increasing prevalence of screening, it is likely that progressively more people will be diagnosed with stage I NSCLC, and thus it is critical to compare the cost-effectiveness of these treatments. METHODS: A Markov model was created to compare the cost-effectiveness of SBRT with WR and lobectomy for MO and CO patients, respectively. Disease, treatment, and toxicity data were extracted from the literature and varied in sensitivity analyses. A payer (Medicare) perspective was used. RESULTS: In the base case, SBRT (MO cohort), SBRT (CO cohort), WR, and lobectomy were associated with mean cost and quality-adjusted life expectancies of $42,094/8.03, $40,107/8.21, $51,487/7.93, and $49,093/8.89, respectively. In MO patients, SBRT was the dominant and thus cost-effective strategy. This result was confirmed in most deterministic sensitivity analyses as well as probabilistic sensitivity analysis, in which SBRT was most likely cost-effective up to a willingness-to-pay of more than $500,000/quality-adjusted life year. For CO patients, lobectomy was the cost-effective treatment option in the base case (incremental cost-effectiveness ratio of $13,216/quality-adjusted life year) and in nearly every sensitivity analysis. CONCLUSIONS: SBRT was nearly always the most cost-effective treatment strategy for MO patients with stage I NSCLC. In contrast, for patients with CO disease, lobectomy was the most cost-effective option.

The aim of this study was to look at the role of alpha 1-acid glycoprotein as a natural anti-inflammatory agent with particular respect to its antineutrophil and anticomplement activity. A recombinantly engineered form of sialyl Lewisx (sLe(x))-bearing alpha 1-acid glycoprotein (sAGP) was administered intravenously to pentobarbital-anesthetized rats after 50 min of intestinal ischemia just before 4 h of reperfusion. A non-sLe(x)-bearing form of AGP (nsAGP) was used as control. sAGP-treated animals had a 62% reduction (P < 0.05) in remote lung injury, assessed by 125I-albumin permeability, compared with those treated with nsAGP (permeability index of 3.61 +/- 0.15 x 10(-3) and 5.18 +/- 0.67 x 10(-3), respectively). There was a reduction in pulmonary myeloperoxidase levels in sAGP-treated rats compared with nsAGP-treated rats. Complement-dependent intestinal injury, assessed by 125I-albumin permeability was reduced by 28% (P < 0.05) in animals treated with sAGP (7.58 +/- 0.63) compared with those treated with nsAGP (10.4 +/- 0.54). We conclude that sAGP ameliorates both complement- and neutrophil-mediated injuries.