Anti-inflammatory activities of two new deoxygenated N-acetyl glucosamines in lipopolysaccharide-activated mouse macrophage RAW264.7 cells.

Background: Glucosamine and N-acetyl-glucosamine (NAG) are amino sugars found in human extracellular matrix with previously described anti-inflammatory effects. Despite mixed results from clinical studies, these molecules have been used extensively in supplements. Objective: We investigated the anti-inflammatory properties of two synthesized derivatives of N-acetyl-glucosamine (NAG), bi-deoxy-N-acetyl-glucosamine (BNAG) 1 and 2. Methods: Using mouse macrophage RAW 264.7 cells with lipopolysaccharide (LPS) to induce inflammation, the effects of NAG, BNAG 1, and BNAG 2 on the expression of IL-6, IL-1ß, inducible nitric oxide synthase (iNOS) and COX-2 were studied using ELISA, Western blot and quantitative RT-PCR. Cell toxicity and nitric oxide (NO) production were evaluated using WST-1 assay and the Griess reagent, respectively. Results: Among the three tested compounds, BNAG1 shows the highest inhibition of iNOS, IL-6, TNF α and IL-1ß expression and NO production. All three tested compounds show slight inhibition on cell proliferation of RAW 264.7 cells, except that BNAG1 displays a remarkable toxicity at the tested maximum dose of 5 mM. Conclusion: BNAG 1 and 2 exhibit notable anti-inflammatory effects compared to the parent NAG molecule.

"No turn back approach" to reduce treatment time for endovascular treatment of acute ischemic stroke.

BACKGROUND: A delay in endovascular treatment is less likely if acute ischemic stroke patients proceed from emergency department (ED) to computed tomographic (CT) scanner and directly to angiographic suite (no turn back approach). We determined the feasibility of the "no turn back approach" and its effect on treatment times and patient outcomes. METHODS: The primary outcomes were procedures performed with a time interval: (1) between ED arrival and microcatheter placement of less than 120 minutes and (2) between CT scan acquisition and microcatheter placement of less than 90 minutes. We determined the effect of the no turn back approach on favorable outcome at discharge. RESULTS: There was a significantly higher rate of CT scan acquisition and microcatheter placement time of less than 90 minutes in patients in whom no turn back approach was used (57.6% versus 31.6%, P = .0007). There was a significantly higher rate of ED arrival to microcatheter placement time of less than 120 minutes in patients in whom no turn back approach was used (31.8% versus 13.7%, P = .004). In the exploratory analysis, there was a trend toward higher rate of favorable outcomes (odds ratio 1.6, 95% confidence interval .9-2.8, P = .07) among those treated with no turn back approach after adjusting for age, admission National Institutes of Health Stroke Scale score strata, congestive heart failure, and diabetes mellitus. CONCLUSIONS: The no turn back approach appeared to be feasible and reduced the time interval between ED arrival and microcatheter placement in acute ischemic stroke patients undergoing endovascular treatment.

Factors associated with favorable response to hyperbaric oxygen therapy among patients presenting with iatrogenic cerebral arterial gas embolism.

BACKGROUND: Iatrogenic cerebral arterial gas embolism (CAGE) is an uncommon but potentially a fatal condition. Hyperbaric oxygen (HBO2) therapy is the only definitive treatment for patients with CAGE presenting with acute neurologic deficits. METHODS: We reviewed medical records and neuroimaging of consecutive CAGE patients treated with HBO2 at a state referral hyperbaric facility over a 22-year period. We analyzed the effect of demographics, source of intra-arterial gas, signs and symptoms, results of imaging studies, time between event and HBO2 treatment, and response to HBO2 treatment in 36 consecutive patients. Favorable outcome was defined by complete resolution or improvement of CAGE signs and symptoms at 24 h after HBO2 treatment. Unfavorable outcome was defined by unchanged or worsened neurologic signs and symptoms or in hospital death. RESULTS: A total of 26 (72%) of the 36 patients had favorable outcome. Patients with favorable outcome were younger compared to those with unfavorable outcome (mean age [years, SD] 44.7 ± 17.8 vs. 58.1 ± 24.1, p = 0.08). Cardiopulmonary symptoms were significantly more common in CAGE related to venous source of gas compared to arterial source (p = 0.024) but did not influence the rate of favorable outcomes. Adjusted multivariate analysis demonstrated that time from event to HBO2 ≤ 6 h (positively) and the presence of infarct/edema on head computerized tomography (CT)/magnetic resonance imaging (MRI) before HBO2 (negatively) were independent predictors of favorable outcome at 24 h after HBO2 treatment [odds ratio (OR) 9.08 confidence interval (CI) (1.13-72.69), p = 0.0376, and (OR) 0.034 (CI) (0.002-0.58), p = 0.0200, respectively]. Two of the 36 patients were treated with thrombolytics because of acute focal deficits and suspected ischemia-one with intravenous and the second with intra-arterial thrombolysis. The latter patient developed fatal intracerebral hemorrhage. CONCLUSIONS: A high proportion of CAGE patients treated with HBO2 had favorable outcomes. Time-to-HBO2 ≤ 6 h increased the odds of favorable outcome, whereas the presence of infarct/edema on CT/MRI scan before HBO2 reduced the odds of a favorable outcome. Timely diagnosis and differentiation from thrombo-embolic ischemic events appears to be an important determinant of successful HBO2 treatment.