Cardiac-specific suppression of NF-κB signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system.

Activation of NF-κB signaling in the heart may be protective or deleterious depending on the pathological context. In diabetes, the role of NF-κB in cardiac dysfunction has been investigated using pharmacological approaches that have a limitation of being nonspecific. Furthermore, the specific cellular pathways by which NF-κB modulates heart function in diabetes have not been identified. To address these questions, we used a transgenic mouse line expressing mutated IκB-α in the heart (3M mice), which prevented activation of canonical NF-κB signaling. Diabetes was developed by streptozotocin injections in wild-type (WT) and 3M mice. Diabetic WT mice developed systolic and diastolic cardiac dysfunction by the 12th week, as measured by echocardiography. In contrast, cardiac function was preserved in 3M mice up to 24 wk of diabetes. Diabetes induced an elevation in cardiac oxidative stress in diabetic WT mice but not 3M mice compared with nondiabetic control mice. In diabetic WT mice, an increase in the phospholamban/sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 ratio and decrease in ryanodine receptor expression were observed, whereas diabetic 3M mice showed an opposite effect on these parameters of Ca(2+) handling. Significantly, renin-angiotensin system activity was suppressed in diabetic 3M mice compared with an increase in WT animals. In conclusion, these results demonstrate that inhibition of NF-κB signaling in the heart prevents diabetes-induced cardiac dysfunction through preserved Ca(2+) handling and inhibition of the cardiac renin-angiotensin system.

EUS for detection of the hepatocellular carcinoma: results of a prospective study.

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) and accurate determination of the number of lesions are critical in determining eligibility for liver transplantation or resection. Current diagnostic modalities (CT and magnetic resonance imaging [MRI]) often miss small lesions. OBJECTIVE: To compare the accuracy of the EUS with CT for the detection of primary tumors of the liver. DESIGN: Prospective single-center study. SETTING: Academic medical center. PATIENTS: Subjects at high risk of HCC (hepatitis B, hepatitis C, or alcoholic cirrhosis) were enrolled. INTERVENTIONS: US, CT, MRI, and EUS examinations of the liver were performed. Liver lesions identified during EUS underwent EUS-guided FNA (EUS-FNA). RESULTS: Seventeen patients were enrolled in the study. Nine of these patients had liver tumors (HCC, 8; cholangiocarcinoma, 1). EUS-FNA established a tissue diagnosis in 8 of the 9 cases. The diagnostic accuracy of US, CT, MRI, and EUS/EUS-FNA were 38%, 69%, 92%, and 94%, respectively. EUS detected a significantly higher number of nodular lesions than US (P = .03), CT (P = .002), and MRI (P = .04). For HCC lesions, a trend was observed in favor of EUS for the detection of more lesions than US (8 vs 2; P = .06) and CT (20 vs 8; P = .06). No complications were observed as a result of EUS-FNA. LIMITATIONS: Small sample size. CONCLUSIONS: EUS-FNA is a safe and accurate test for the diagnosis of HCC. EUS increases the accuracy of intrahepatic staging of the HCC by delineation of lesions, which are missed by CT and MRI. We recommend EUS for suspected HCC, particularly in cases that are being considered for liver transplantation.