Ascorbic acid and hydrocortisone synergistically inhibit septic organ injury via improving oxidative stress and inhibiting inflammation.

BACKGROUND: The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism. METHOD: Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides. RESULTS: AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing alanine aminotransferase, aspartate aminotransferase, serum urea nitrogen, and serum creatinine and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1ß, and IL-6 and regulating MDA, SOD, and GSH. In an in vitro study, cotreatment of RAW 264.7 macrophages with Hyd and AscA sharply reduced reactive oxygen species (ROS) generation and synergistically inhibited TNF-α, IL-1ß, and IL-6 secretion, which could be abolished by additional stimulation with the ROS donor 3-nitropropionic acid (3-NP). As expected, cotreatment of macrophages with Hyd and AscA synergistically inhibited the activation of p38 MAPK and p-p65, and the effect could be reversed by additional stimulation with 3-NP. CONCLUSIONS: AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.

Endovascular management strategy for patients with acute occlusive internal carotid artery dissection combined with tandem middle cerebral artery occlusion / 中华神经医学杂志

Objective To investigate the endovascular management strategy for patients with acute occlusive internal carotid artery (ICA) dissection combined with tandem middle cerebral artery (MCA) occlusion,and assess its safety and outcomes.Methods Six ICA dissection patients with tandem middle cerebral artery occlusion,admitted to our hospital from March 2011 to December 2012,were treated with endovascular treatment.Recanalization of ICA dissection and Solitaire AB stent thrombectomy for MCA occlusion were achieved in acute stage.Endovascular stent therapy for ICA dissection was performed in stable phase.The clinical data and the results of treatment of these patients were retrospectively analyzed.Results Successful recanalization of MCA was obtained in all 6 patients; one ICA dissection was recanalized by Solitaire AB stent (6 mm×20 mm) and four ICA dissections were recanalized by 6F guiding catheter introduced by microcatheter; in the other one patient with tortuosity of ICA,recanalization of dissection was failed but recanalizztion was achieved one month after anticoagulation and antiplatelet; five patients accepted successful endovascular stent therapy for ICA dissection in the second phase.The mean National Institutes of Health Stroke Scales (NIHSS) scores were four points two weeks after procedure,which showed obvious increase as compared with those before procedure (16 points).Angiography showed MCA was patent after six months in two patients and dissection recovered completely by stent.All patients got follow-up in the Out-patient Department and no patient suffered a new ischemic stroke.Five patients had good mRS scores (≤ 2) with only one reaching 3 points.Conclusion Solitaire stent thrombectomy for MCA occlusion in acute stage,followed by endovascular stent therapy for ICA dissection in stable phase,may be an effective,safe and attractive treatment for tandem MCA occlusion combined with ICA dissection.