No abstract

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.

The aim of this study was to look at the role of α1-acid glycoprotein as a natural anti-inflammatory agent with particular respect to its antineutrophil and anticomplement activity. A recombinantly engineered form of sialyl Lewisx(sLex)-bearing α1-acid glycoprotein (sAGP) was administered intravenously to pentobarbital-anesthetized rats after 50 min of intestinal ischemia just before 4 h of reperfusion. A non-sLex-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 × 10−3 and 5.18 ± 0.67 × 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.

Background: Complete pulmonary metastasectomy for sarcoma metastases provides patients an opportunity for long-term survival and possible cure. Intraoperative localization of preoperatively identified metastases and identification of occult lesions can be challenging. In this trial we evaluate the efficacy of near-infrared (NIR) intraoperative imaging using "second window" indocyanine-green (ICG) during metastasectomy to identify known metastases and to detect occult nodules. Methods: Thirty subjects with pulmonary nodules suspicious for sarcoma metastases were enrolled in an open-label, feasibility study (NCT02280954). All subjects received intravenous ICG (5mg/kg) 24 hours prior to metastasectomy. Subjects 1-10 (Cohort 1) underwent metastasectomy via thoracotomy to assess fluorescence patterns of nodules detected by traditional methods (preoperative imaging and intraoperative visualization/bimanual palpation). After confirming reliability within Cohort 1, Subjects 11-30 (Cohort 2) underwent VATS metastasectomy with NIR imaging. Results: In Cohort 1, 14/16 (87.5%) of preoperatively identified pulmonary metastases displayed tumor fluorescence. Non-fluorescent metastases were deeper than fluorescent metastases (2.1cm vs 1.3cm; p=0.03). 5/5 metastases identified during thoracotomy displayed fluorescence. NIR imaging identified 3 additional occult lesions in this cohort. In Cohort 2, 33/37 (89.1%) known pulmonary metastases displayed fluorescence. Non-fluorescent tumors were deeper than 2.0cm