Axonal degeneration is a major cause of permanent neurological deficit in multiple sclerosis (MS), but no current therapies for the disease are known to be effective at axonal protection. Here, we examine the ability of a sodium channel–blocking agent, flecainide, to reduce axonal degeneration in an experimental model of MS, chronic relapsing experimental autoimmune encephalomyelitis (CR‐EAE). Rats with CR‐EAE were treated with flecainide or vehicle from either 3 days before or 7 days after inoculation (dpi) until termination of the experiment at 28 to 30 dpi. Morphometric examination of neurofilament‐labeled axons in the spinal cord of CR‐EAE animals showed that both flecainide treatment regimens resulted in significantly higher numbers of axons surviving the disease (83 and 98% of normal) compared with controls (62% of normal). These findings indicate that flecainide and similar agents may provide a novel therapy aimed at axonal protection in MS and other neuroinflammatory disorders.
P63 and p73 are two homologues of the important tumor suppressor gene p53. In this study, we investigated p63 and p73 expression by immunocytochemistry using antibodies for TAp73 and p634A4 isoforms in 91 highgrade and 107 low-grade squamous intraepithelial lesions, 212 atypical squamous cells of undetermined significance, 9 squamous cell carcinomas and 63 normal samples from an Asian screening population together with 47 hospital samples of carcinomas. There was significant correlation between the TAp73 and p634A4 indices (Po0.0001). Significantly, higher TAp73 and p634A4 indices were found in high-grade lesions or carcinoma when compared with atypical squamous cells and low-grade lesions (Po0.0001). Among atypical squamous cells, p634A4 indices of cases that subsequently progressed to low-grade (P ¼ 0.031) or high-grade lesions (P ¼ 0.006) were significantly higher than those that did not. For atypical squamous cells positive for high-risk human papillomavirus (HPV) as detected by Digene (61%), cases with high p634A4 index were still more likely to have subsequent high-grade lesions detected (P ¼ 0.016). Among low-grade lesions, significantly higher TAp73 (P ¼ 0.038) was found in cases that subsequently progressed to high-grade lesions. There was significant correlation between presence of high-risk HPV and p634A4 index (P ¼ 0.01). In summary, p63 and p73 immunocytochemistry are potential good markers for detection of carcinoma and high-grade lesions in cervical cytology samples and for triage management of women with atypical squamous cells and low-grade Cervical cytology screening is effective in the prevention of cervical cancer by detecting asymptomatic cervical cancer and its precursors although there is limitation in its sensitivity and specificity. 1 Among cytological abnormalities detectable in a screening population, atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL), especially the former, are the most common diagnostic categories. [2][3][4] Both were associated with a higher possibility of subsequent development of cervical cancer when compared with women with negative cytology. 3 Colposcopic examination of all such cases poses significant demand on the community resources. To improve the efficiency of cervical cancer screening, human papillomaviruses (HPV) DNA testing has been introduced for the triage of women with ASC-US and for primary screening. 5,6 Although HPV test shows high sensitivity, additional markers are necessary to improve the specificity of identifying cervical cancers or high-grade precursors. [7][8][9][10][11] It is also necessary to discover adjunct markers for management of LSIL as HPV testing is not so effective in triage management of LSIL.
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