Role of migratory inhibition factor in age-related susceptibility to radiation lung injury via NF-E2-related factor-2 and antioxidant regulation.

Microvascular injury and increased vascular leakage are prominent features of radiation-induced lung injury (RILI), and often follow cancer-associated thoracic irradiation. Our previous studies demonstrated that polymorphisms in the gene (MIF) encoding macrophage migratory inhibition factor (MIF), a multifunctional pleiotropic cytokine, confer susceptibility to acute inflammatory lung injury and increased vascular permeability, particularly in senescent mice. In this study, we exposed wild-type and genetically engineered mif(-/-) mice to 20 Gy single-fraction thoracic radiation to investigate the age-related role of MIF in murine RILI (mice were aged 8 wk, 8 mo, or 16 mo). Relative to 8-week-old mice, decreased MIF was observed in bronchoalveolar lavage fluid and lung tissue of 8- to 16-month-old wild-type mice. In addition, radiated 8- to 16-month-old mif(-/-) mice exhibited significantly decreased bronchoalveolar lavage fluid total antioxidant concentrations with progressive age-related decreases in the nuclear expression of NF-E2-related factor-2 (Nrf2), a transcription factor involved in antioxidant gene up-regulation in response to reactive oxygen species. This was accompanied by decreases in both protein concentrations (NQO1, GCLC, and heme oxygenase-1) and mRNA concentrations (Gpx1, Prdx1, and Txn1) of Nrf2-influenced antioxidant gene targets. In addition, MIF-silenced (short, interfering RNA) human lung endothelial cells failed to express Nrf2 after oxidative (H2O2) challenge, an effect reversed by recombinant MIF administration. However, treatment with an antioxidant (glutathione reduced ester), but not an Nrf2 substrate (N-acetyl cysteine), protected aged mif(-/-) mice from RILI. These findings implicate an important role for MIF in radiation-induced changes in lung-cell antioxidant concentrations via Nrf2, and suggest that MIF may contribute to age-related susceptibility to thoracic radiation.

Intramural blood pools accompanying aortic intramural hematoma: CT appearance and natural course.

PURPOSE: To evaluate multidetector computed tomographic (CT) images to investigate the prevalence, morphology, natural course, and prognostic effect of intramural blood pools (IBPs) in patients with acute intramural hematoma (IMH). MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Sixty-five patients (41 men; mean age, 65.9 years ± 11.3 [standard deviation]) with acute IMH undergoing three or more multidetector CT examinations during follow-up for 12 months or longer (median = 18 months), except for those undergoing surgery (n = 16), were enrolled. Associated factors of developing and resorption of IBP in IMH were analyzed by using logistic regression. RESULTS: There were 40 IBPs in 10 patients at initial multidetector CT, and 15 new IBPs developed in 11 patients during follow-up. IBPs occurred most in the descending thoracic (55% [31 of 56]) and abdominal (41% [23 of 56]) aorta in 28% (18 of 65) of patients. During 33.8 months (range, 2.8-50 months) of follow-up in these 18 patients, 57% (32 of 56) of IBPs showed complete resorption in 15 patients, 29% (16 of 56) of IBPs showed incomplete resorption in eight patients, and 14% (eight of 56) of IBPs had interrupted follow-up because of surgery or death in three patients. Logistic regression showed that age younger than 70 years (odds ratio [OR], 8.74; 95% confidence interval [CI]: 1.03, 76.9) and IMH wall thickness greater than 10 mm (OR, 4.93; 95% CI: 1.04, 23.0) were associated with developing IBP at initial multidetector CT, while IBP with larger transmural diameter (OR, 1.16; 95% CI: 1.02, 1.31) and multidetector CT-demonstrated connection with intercostal or lumbar artery (63% [35 of 56]) (OR, 5.44; 95% CI: 1.43, 20.9) were associated with incomplete resorption. CONCLUSION: IBPs are frequently observed at multidetector CT in patients with IMH. They may resolve over time or appear during follow-up. These findings are not associated with a poor prognosis, and IBPs should be distinguished from ulcerlike projections.

TIPS in patients with cranial porta hepatis: ultrasound-guided transhepatic portohepatic-portocaval puncture in single needle pass.

OBJECTIVE: The purpose of this study was to describe our technique of transhepatic serial puncture of the portal vein and hepatic vein-inferior vena cava in one needle pass under ultrasound guidance to place a transjugular intrahepatic portosystemic shunt (TIPS) in patients with a porta hepatis cranial to the usual location. MATERIALS AND METHODS: Six patients (five men, one woman) underwent transhepatic TIPS procedures at our institution. The indications for portal decompression were recurrent variceal bleeding in four patients and refractory ascites and hydrothorax in one patient each. In five patients initial attempts at a classic transjugular approach failed because of an unusual angle between the hepatic vein and the portal vein; in the other patient, revision of an occluded shunt had failed. Two patients had main portal vein thrombosis. RESULTS: Technical success was achieved in all six patients. Two patients received a portohepatic venous shunt and four a portocaval shunt (inferior vena cava to right portal vein in three patients and inferior vena cava to left portal vein in one patient).The portosystemic pressure gradient before TIPS was 17-35 mm Hg and after TIPS was 6-10 mm Hg. No procedure-related complications occurred. One patient had severe hepatic encephalopathy. Two patients had shunt occlusion, which was successfully revised 17 and 10 months after the procedure. CONCLUSION: Our technique is a safe, effective, and universally applicable method for establishment of a TIPS in patients with either normal venous anatomy or severely distorted liver parenchyma.