Digital infrared thermal imaging might be helpful in evaluating the inflammatory state of GO and the follow-up effect of methylprednisolone pulse therapy.
Although previous studies have indicated that the neuroprotective effect of N-acetylcysteine (NAC) required activation of the Ras-extracellular-signal-regulated kinase (ERK) pathway, the detailed mechanisms and signal cascades leading to activation ERK are not clear. In the present study, we investigated the effect of NAC on A beta(25-35)-induced neuronal death. Pretreatment of neurons with NAC 1 hr before application of A beta prevented A beta-mediated cell death. NAC increased cyclin-dependent kinase 5 (Cdk5) phosphorylation, an effect that was blocked by Cdk5 inhibitor. The neuroprotective effect of NAC was significantly attenuated by Cdk5 inhibitors or in neurons transfected with Cdk5 or p35 small interfering RNA (siRNA). Conversely, pretreatment of neurons with the calpain inhibitors calpeptin or MDL28170 enhanced the neuroprotective effect of NAC. A beta(25-35) caused a significant decrease in the level of p35, with a concomitant increase in p25, which was completely prevented by NAC. This effect of NAC was blocked by the Cdk5 inhibitors roscovitine and butyrolactone. In addition, NAC increased Cdk5/p35 kinase activity but reduced Cdk5 kinase activity. A beta(25-35) treatment decreased phosphorylated levels of ERK, which could be reversed by NAC. The effect of NAC was completely blocked by Cdk5 inhibitors. NAC reversed the A beta(25-35)-induced decrease in the expression of Bcl-2, which could be blocked by the MAPK kinase (MEK) inhibitor or Cdk5 inhibitors. These results suggest that NAC-mediated neuroprotection against A beta toxicity is likely mediated by the p35/Cdk5-ERKs-Bcl-2 signal pathway.
ABSTRACT.Purpose: Graves' ophthalmopathy (GO) involves autoimmune process resulting in proptosis, congestion, oedema and diplopia. Werner's NOSPECS classification and clinical activity score (CAS) of GO cannot objectively describe the inflammatory status. Digital infrared thermal imaging (DITI) detects local temperature and may reflect the degree of orbital inflammation. The aim of this study was to evaluate the clinical application of the eye temperature measured by DITI.Methods: Forty-six patients with GO receiving intravenously methylprednisolone pulse therapy (MPT) were included in this study. Local temperatures of the lateral orbit, upper eyelid, inner caruncle, medial conjunctiva, lateral conjunctiva, lower eyelid and cornea were measured with DITI before and after MPT. CAS, proptosis, eye movement (EOM) and diplopia were also recorded. Improvement of CAS was defined as at least one point decrease at either side of the eye, which was 0.5 score decrease as to the average of bilateral CAS.Results: Local temperatures of the eyes decreased after MPT. The mean value of temperature (MT) of 12 points including the lateral orbit, upper eyelid, inner caruncle, medial conjunctiva, lateral conjunctiva and lower eyelid of both eyes before MPT was 32.65°. The mean change of MT after MPT (4T) was )0.22°. 4T significantly negative-correlated with basal MT (correlation coefficient = )0.54, p = 0.004). Higher baseline MT and CAS before MPT correlated with higher possibility of improvement of CAS after MPT (p = 0.013 and 0.012, respectively). Baseline MT and CAS together correlated with improvement of CAS after MPT better than baseline CAS alone could do (area under the receiver operating characteristic curve: 82.81% and 66.63%, respectively).Conclusions: Basal temperature of the eyes measured by DITI was an objective indicator of inflammation of GO. Combining CAS and MT could better predict the outcome of MPT than CAS alone.
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