BackgroundAcetaminophen (APAP) hepatotoxicity is associated with a high rate of gram-negative enteric bacterial infection; however, the underlying mechanism is still unknown. APAP overdose induces massive hepatocyte necrosis, necrotic tissue releases high mobility group B1 (HMGB1) and exogenous HMGB1 is able to induce gut bacterial translocation (BT) in normal mice; therefore, it is possible that HMGB1 mediates gut BT in APAP hepatotoxicity. This study aims to test this hypothesis by using anti-HMGB1 neutralizing antibody to treat APAP overdose for 24-48 hours.MethodsMale C57BL/6 mice were intraperitoneally (i.p.) injected with a single dose of APAP (350 mg/kg dissolved in 1 mL sterile saline). 2 hrs after APAP injection, the APAP challenged mice were randomized to receive treatment with either anti-HMGB1 antibody (400 μg per dose) or non-immune (sham) IgG every 24 h for a total of 2 doses.Results24 and 48 hrs after APAP challenge, anti-HMGB1 treatment instead of sham IgG therapy significantly decreased serum HMGB1 concentrations and reduced BT by 85%; serum HMGB1 levels were positively correlated with the amount of BT; anti-HMGB1 therapy decreased hepatic BT at 48 h, which was associated with better recovered liver structure and better restored hepatic immune system that was shown by enhanced hepatic mRNA expression of TNF-α, IL-6 and extensive proliferation of inflammatory and reticuloendothelial cells; however, anti-HMGB1 treatment did not decrease gut mucosal permeability as compared to the sham IgG therapy at either 24 or 48 hrs.ConclusionHMGB1 neutralization is associated with bacterial translocation during APAP hepatotoxicity.

During a 10-year period, intraparenchymal aneurysms were found in 38 of 748 patients at selective abdominal angiography with magnification technique. According to strict criteria, 17 patients were classified as suffering from necrotizing vasculitis of the polyarteritis nodosa group (PAN), 7 from severe arterial hypertension, and 3 from rheumatoid arthritis. The diagnoses of 5 patients remained to be confirmed, and each of the remaining 6 patients suffered from various other diseases. PAN was diagnosed histopathologically in 2 patients without angiographic aneurysms. Based on the 156 patients in whom the indication for angiography was suspicion of arteritis, the angiographic diagnosis of PAN had a sensitivity of 89 percent and a specificity of 90 percent, a positive predictive value of 55 percent and a negative predictive value of 98 percent. The mean number of both renal and hepatic aneurysms was higher in patients with PAN than in the other patients (p < 0.01 and p < 0.05, respectively). Five PAN patients had numerous and large aneurysms, whereas the aneurysms of the other 12 PAN patients did not differ from those of patients with other diseases. Patients with PAN had renal infarcts more often than the other patients (p < 0.05). Our findings suggest that visceral angiography is useful in establishing the diagnosis of PAN, but the angiographic finding of aneurysms is not pathognomonic.

BackgroundAcetaminophen (APAP) overdose induces massive hepatocyte necrosis. Liver regeneration is a vital process for survival after a toxic insult. Since hepatocytes are mostly in a quiescent state (G0), the regeneration process requires the priming of hepatocytes by cytokines such as TNF-α and IL-6. Ringer's lactate solution (RLS) has been shown to increase serum TNF-α and IL-6 in patients and experimental animals; in addition, RLS also provides lactate, which can be used as an alternative metabolic fuel to meet the higher energy demand by liver regeneration. Therefore, we tested whether RLS therapy improves liver recovery after APAP overdose.MethodsC57BL/6 male mice were intraperitoneally injected with a single dose of APAP (300 mg/kg dissolved in 1 mL sterile saline). Following 2 hrs of APAP challenge, the mice were given 1 mL RLS or Saline treatment every 12 hours for a total of 72 hours.Results72 hrs after APAP challenge, compared to saline-treated group, RLS treatment significantly lowered serum transaminases (ALT/AST) and improved liver recovery seen in histopathology. This beneficial effect was associated with increased hepatic tissue TNF-α concentration, enhanced hepatic NF-κB DNA binding and increased expression of cell cycle protein cyclin D1, three important factors in liver regeneration.ConclusionRLS improves liver recovery from APAP hepatotoxicity.

IgG4-positive ascending aortic wall was frequent in our study cohort (13%) and revealed aortic inflammation associated with dilatation.