Imaging of lower extremity trauma from Boston Marathon bombing.

The goal of this study is to describe the imaging features of lower extremity blast injuries in patients encountered in the radiology departments from the Boston Marathon bombings. A total of 115 patients presented to four acute care hospitals on April 15, 2013, 43 of whom presented with lower extremity injuries and were included in this study. The imaging findings of primary, secondary, tertiary, and quaternary blast injuries were evaluated. Forty-one of 43 patients sustained secondary blast injuries to the lower extremities with 31 patients (70 %) having retained shrapnel, seven patients (16 %) having soft tissue lacerations without retained shrapnel, and ten patients (23 %) having lower extremity amputation (7 % double amputees). Eight of these patients (20 %) had lower extremity fractures, and five patients (12 %) had vascular injuries. Two of the 43 patients (5 %) had only tertiary injuries, and five of 43 patients (12 %) were noted to have lower extremity burns, consistent with quaternary blast injury. No primary blast injury occurred in the lower extremities. A vast majority of lower extremity injuries were from secondary blast injury, most commonly from retained shrapnel in 70 % of patients and 23 % of patients sustaining lower extremity amputation. Retained shrapnel in the lower extremity was most commonly ball bearings and pressure cooker fragments, and most injuries affected the leg, followed by the thigh and foot.

Oltipraz, 3H-1,2-dithiole-3-thione, and sulforaphane induce overlapping and protective antioxidant responses in murine microglial cells.

Oltipraz (OPZ) is a known inducer of glutathione S-transferases and a mechanism-based inhibitor of cytochrome P450 1A2. Given the detoxification characteristics of this compound, the transcriptional effects of OPZ, along with the related naturally occurring compounds 3H-1,2-dithiole-3-thione (D3T) and sulforaphane (SF), were examined by gene expression profiling in murine BV-2 microglial cells, a neuronal macrophage cell type that mediates inflammatory responses in the brain. We show that the three compounds generate largely overlapping transcriptional changes in genes that are associated with detoxification and antioxidant responses. In addition, induction of an antioxidant/detoxification response in the microglial cells by OPZ, D3T, or SF was also able to protect cells from H2O2 -induced toxicity and to attenuate the production of reactive oxygen species in response to lipopolysaccharide treatment of cells. These results show that OPZ, D3T, and SF activate overlapping changes in gene expression and that they can regulate detoxification/antioxidant responses in multiple cells types, including cell types known to have a role in the production of oxidative stress.

Oltipraz inhibits inducible nitric oxide synthase in vitro and inhibits nitric oxide production in activated microglial cells.

The clinically relevant drug oltipraz (OPZ) has previously been shown to inhibit cytochrome P450 enzymes [Chem. Res. Toxicol. 13 (2000) 245]. The current study reveals that OPZ is also able to inhibit *NO formation by purified inducible nitric oxide synthase (iNOS) but not by neuronal nitric oxide synthase in hemoglobin assays. The inhibition of iNOS by OPZ is reversible and competitive with an IC(50) of 5.9 microM and Ki of 0.6 microM. In murine BV-2 microglial cells, an immortalized cell line that produces *NO in response to lipopolysaccharide (LPS), OPZ is able to block the formation of nitrite in LPS treated cells. The inhibitory effect of OPZ on LPS treated cells is not due to cell toxicity. Finally, treatment of cells with OPZ does not induce or suppress expression of iNOS protein as shown by Western blot analysis.