A case of acute disseminated encephalomyelitis following human papillomavirus quadrivalent vaccination.

Acute disseminated encephalomyelitis is a rare autoimmune demyelinating disease associated with preceding infection or vaccination. Herein, we report a case of refractory fulminant acute disseminated encephalomyelitis that occurred 25 days after Gardasil vaccination (Merck).

Associations of cigarette smoking with intracranial atherosclerosis in the patients with acute ischemic stroke.

BACKGROUND: Although cigarette smoking has been established as an important risk factor for stroke, the effect on the atherosclerotic stenosis, which are based on observational studies, have been controversial. We set out to examine the differences in the risk factors between smokers and nonsmokers and to investigate the association of cigarette smoking with cerebral arterial stenosis. METHODS: A total of 989 consecutive patients with acute noncardioembolic ischemic stroke were prospectively enrolled from June 2004 to January 2010. The risk factor profiles were compared between smokers and nonsmokers. We analyzed the degree of stenosis in all MRA, and evaluated influencing factors in the patients with intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) who were randomly matched by age and sex. RESULTS: There were differences in the distribution of risk factors between the 467 (70.0%) nonsmokers and the 215 (30.0%) smokers. Nonsmokers were older (71.7±11.0 versus 61.7±12.0, p<0.001) and had a higher frequency of hypertension than smokers had (75.4% versus 64.0%, p=0.002). When smokers and nonsmokers were age- and sex-matched, smoking was more prevalent in patients with ICAS than with ECAS (32.9% versus 28.2%). Conditional regression analysis revealed that smoking and hypertension increased the odds of ICAS [smoking, odds ratio (OR): 1.83, p=0.026; hypertension, OR: 1.84, p=0.01], whereas hyperlipidemia increased the odds of ECAS (OR: 1.87, p=0.034). CONCLUSION: The distributions of the major risk factors for ischemic stroke were different between smokers and nonsmokers. Cigarette smoking may be more associated with ICAS than with ECAS after adjusting for potential risk factors.

Phosphatidylinositol 3-kinase activator reduces motor neuronal cell death induced by G93A or A4V mutant SOD1 gene.

The primary pathogenic mechanism of amyotrophic lateral sclerosis (ALS) remains largely unclear. We recently observed that motoneuron cell death mediated by G93A or A4V mutant SOD1, causing familial ALS, was related with decrease of survival signals, such as phosphatidylinositol 3-kinase (PI3-K) and Akt, which play a pivotal role in neuronal survival. Using a G93A or A4V mutant SOD1 transfected VSC4.1 motoneuron cells (G93A or A4V cells, respectively), we presently investigated whether PI3-K activator could reduce mutant SOD1-mediated motoneuron cell death. To investigate the effect of PI3-K activator on viability of G93A and A4V cells, these cells were treated with 10, 50 or 100ng/ml PI3-K activator for 24h and viability and intracellular signals, including Akt, glycogen synthase kinase-3 (GSK-3), heat shock transcription factor-1 (HSTF-1), cytosolic cytochrome c, caspase-3 and poly(ADP-ribose) polymerase (PARP), were compared with those without treatment (control). Compared with non-treated control G93A or A4V cells, the PI3-K activator treatment increased their viability by enhancing the survival signals, including pAkt, pGSK-3, and by inhibiting the death signals, including caspase-3 activation and PARP cleavage. These results suggest that PI3-K activator protects G93A or A4V cells from mutant SOD1-mediated motoneuron cell death by both activating survival signals and inactivating death signals.

Protective effect of diallyl disulfide on oxidative stress-injured neuronally differentiated PC12 cells.

The effects of diallyl disulfide (DADS), a garlic-derived compound, on the viability of neuronal cells and cell signals, including phosphatidylinositol 3-kinase (PI3K)/Akt, glycogen synthase kinase-3 (GSK-3), cytochrome c, caspase-3, and poly(ADP-ribose) polymerase (PARP), were investigated in PC12 cells neuronally differentiated by nerve growth factor. To evaluate the toxicity of DADS itself, nPC12 cells were treated with several concentrations of DADS, and 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue stain revealed that the viability was not affected by low concentration of DADS, up to 20 microM, but it was decreased at higher than this concentration. The levels of free radicals and membrane lipid peroxidation were significantly increased in nPC12 cells when treated with more than 50 microM DADS, and treatment of PC12 cells with 100 microM DADS killed the cells by inhibiting PI3K/Akt and by promoting activation of GSK-3 and caspase-3, release of cytochrome c, and cleavage of PARP. To evaluate the protective effects of low concentration of DADS on oxidative stress-injured nPC12 cells, the viability of the cells (pretreated with DADS for 2 h vs. not pretreated) was evaluated 24 h after exposure to 100 microM H2O2 for 30 min. Compared to the cells treated with 100 microM H2O2 only, pretreatment of the cells with 20 microM DADS before exposure to 100 microM H2O2 increased the viability and induced activation of PI3K and Akt, inactivation of GSK-3, and inhibition of cytochrome c release, caspase-3 activation, and PARP cleavage. These results indicate that low concentration of DADS has neuroprotective effects by activating PI3K/Akt and by inhibiting GSK-3 activation, cytochrome c release, caspase-3 activation, and PARP cleavage, whereas high concentration is rather cytotoxic. Therefore, some specific optimum concentration of DADS may be a new potential therapeutic strategy for oxidative stress injured in vitro model of neurodegenerative diseases.