Combined therapy of intensive statin plus intravenous rt-PA in acute ischemic stroke: the INSPIRE randomized clinical trial.

OBJECTIVE: To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. METHODS: A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. RESULTS: The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran-Mantel-Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). CONCLUSION: The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642.

Analysis of the characteristics of persistent postural-perceptual dizziness: A clinical-based study in China.

OBJECTIVE: Persistent postural-perceptual dizziness (PPPD) is a common cause of chronic dizziness, but only a few studies have reported its clinical characteristics, and no related research has been performed in China. Therefore, the purpose of this study was to analyze the characteristics of PPPD for the first time in China. DESIGN: Data was collected from all patients during standard clinical practice, and further to evaluate the characteristics of PPPD comparing with the control group. STUDY SAMPLE: A total of 43 patients diagnosed with PPPD were selected as the study group for analysis. RESULTS: Women were significantly more represented in the study group than men, and in the majority of cases the age of onset was in middle-age, and sleep quality was clearly decreased compared with controls, with more statistically significantly higher levels of anxiety. Personality analysis identified that neuroticism was significantly higher than in controls. CONCLUSIONS: In this sample we showed that PPPD was more represented in female patients, the age of onset was 40-60 years old, the majority of patients had sleep disorders, anxiety was the main mood disorder to be identified, and personality analysis found that neurotic personality may be the risk factor for developing PPPD. Further large scale studies are suggested in China.

Protective effects of luteolin against cognitive impairment induced by infusion of Aß peptide in rats.

Luteolin can be found in many traditional Chinese medicines, it's a falconoid compound derived from Lonicera japonica Thunb. This study aims to investigate the neuroprotective effects of luteolin against cognitive impairment induced by amyloid-ß (Aß) peptide and the underlying mechanisms in rats. The animal behavioral tests showed that luteolin could ameliorate Aß-induced learning and memory impairment. In hippocampal tissue, the activity of choline acetyl transferase (ChAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) increased after treated by luteolin. Luteolin also reversed the increased activity of acetylcholine esterase (AchE). In hippocampi homogenate, the content of acetylcholine (Ach) increased, but malondialdehyde (MDA) reduced. Moreover, luteolin can increase Bcl-2/Bax ratio. This study demonstrated that luteolin could protect Alzheimer's disease (AD) rats against Aß-induced cognitive impairment through regulating the cholinergic system and inhibiting oxidative injuries. The results suggesting that luteolin may have potential as a therapy for AD.

Literature Review and Case Report of Intravenous Thrombolysis in Acute Cerebral Infarction Attributed to Cervical Arterial Dissection.

Acute cerebral infarction (ACI) caused by cervical arterial dissection (CAD) is a rare clinical disease. Therapeutic approaches include anticoagulant therapy, antiplatelet aggregation, and thrombolytic therapy. Currently, anticoagulant therapy or antiplatelet aggregation is the primary choice, whereas the thrombolytic therapy is still controversial. In this article, we report a patient with ACI caused by right CAD, which led to a compensatory increase in blood supply to the right middle cerebral artery through the anterior communicating artery. After treatment with intravenous thrombolysis, the clinical symptoms of the patient improved, and the National Institutes of Health Stroke Scale (NIHSS) score declined to 2 points from the initial 14 points. In addition, cranial computed tomography scans showed that there were no signs of intracranial or extracranial hemorrhage, but that the vessel occlusion was still uncured. After 17 days of antiplatelet aggregation treatment, a cranial magnetic resonance angiography scan showed complete recanalization of the right internal carotid artery. Furthermore, the NIHSS score was reduced to 1 point when the patient discharged, and for 3 months of follow-up.

Increased serum levels of brain-derived neurotrophic factor in autism spectrum disorder.

The aim of this study was to investigate the potential role of brain-derived neurotrophic factor (BDNF) in children with autism spectrum disorders (ASD) by measuring serum circulating levels of BDNF as well as calcium and comparing them with age-matched and sex-matched normal controls. The study included 75 drug-naive ASD children and 75 age-sex-matched healthy children. The concentration of serum BDNF was determined using the enzyme-linked immunosorbent assay method at baseline. Clinical information was collected. The severity of ASD was assessed at admission using the Childhood Autism Rating Scale total score. The results indicated that the mean serum BDNF levels were significantly (P<0.0001) higher in children with ASD compared with the control cases (17.59±5.55 vs. 11.21±2.79 ng/ml; t=8.902). On the basis of the receiver operating characteristic curve, the optimal cutoff value of serum BDNF levels as an indicator for auxiliary diagnosis of autism was projected to be 12.65 ng/ml, which yielded a sensitivity of 80.8% and a specificity of 70.2%; the area under the curve was 0.840 [95% confidence interval (CI), 0.777-0.904]. In univariate logistic regression analysis, with an unadjusted odds ratio of 9.42 (95% CI, 4.33-25.95; P<0.0001), BDNF of 12.65 ng/ml or more had an association with a diagnosis of ASD. After adjusting for possible covariates, BDNF of 12.65 ng/ml or more is still an independent indicator of ASD, with an adjusted odds ratio of 7.33 (95% CI, 2.98-16.55; P<0.0001). Serum BDNF levels may be associated independently with the severity of ASD, and higher BDNF levels could be considered an independent diagnostic marker of ASD.

Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia.

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potential molecular mechanisms in cerebral ischemia rats. We found that sulforaphane significantly attenuated the blood-brain barrier (BBB) disruption; decreased the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1ß; reduced the nitric oxide (NO) levels and inducible nitric oxide synthase (iNOS) activity; inhibited the expression of iNOS and cyclooxygenase-2 (COX-2). In addition, sulforaphane inhibits the expression of p-NF-κB p65 after focal cerebral ischemia-reperfusion injury. Taken together, our results suggest that sulforaphane suppresses the inflammatory response via inhibiting the NF-κB signaling pathway in a rat model of focal cerebral ischemia, and sulforaphane may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

Insulin-like growth factor-1 as a prognostic marker in patients with acute ischemic stroke.

OBJECTIVE: Insulin-like growth factor-1 (IGF-1) has been associated with cardiovascular risk factors and atherosclerosis. The aim of the present study was to evaluate the prognostic value of IGF-1 levels in patients with acute ischemic stroke (AIS). METHODS: All patients with first-ever AIS from August 1, 2012 to August 31, 2013 were recruited to participate in the study. Clinical data were collected. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to serum IGF-1 levels. For the assessment of functional outcome at 90 days Modified Rankin Scale (mRS) was used. On admission, serum IGF-1 levels were determined by chemiluminescence immunoassay. The influence of IGF-1 levels on functional outcome and death was assessed by multivariate logistic regression analysis. RESULTS: Patients with an unfavorable outcomes and non-survivors had significantly decreased serum IGF-1 levels on admission (P<0.0001 for both). IGF-1 was an independent prognostic marker of functional outcome and death [odds ratio 0.89 (0.84-0.93) and 0.90 (0.84-0.95), respectively, P<0.0001 for both, adjusted for age, NIHSS score and other predictors] in patients with ischemic stroke. Serum IGF-1 levels ≤130 ng/mL was as an value indicator for unfavorable functional outcome (OR 3.31, 95% CI:1.87-5.62; P<0.0001), after adjusting for other significant confounders. CONCLUSIONS: We reported a significant association between low serum IGF-1 levels and unfavorable functional outcome and death.

Regulation of adenosine triphosphate-sensitive potassium channels suppresses the toxic effects of amyloid-beta peptide (25-35).

In this study, we treated PC12 cells with 0-20 µM amyloid-ß peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 µM amyloid-ß peptide (25-35) decreased PC12 cell viability, but adenosine triphosphate-sensitive potassium channel activator diazoxide suppressed the decrease in PC12 cell viability induced by amyloid-ß peptide (25-35). Diazoxide protected PC12 cells against amyloid-ß peptide (25-35)-induced increases in mitochondrial membrane potential and intracellular reactive oxygen species levels. These protective effects were reversed by the selective mitochondrial adenosine triphosphate-sensitive potassium channel blocker 5-hydroxydecanoate. An inducible nitric oxide synthase inhibitor, Nω-nitro-L-arginine, also protected PC12 cells from amyloid-ß peptide (25-35)-induced increases in both mitochondrial membrane potential and intracellular reactive oxygen species levels. However, the H2O2-degrading enzyme catalase could not reverse the amyloid-ß peptide (25-35)-induced increase in intracellular reactive oxygen species. A 24-hour exposure to amyloid-ß peptide (25-35) did not result in apoptosis or necrosis, suggesting that the increases in both mitochondrial membrane potential and reactive oxygen species levels preceded cell death. The data suggest that amyloid-ß peptide (25-35) cytotoxicity is associated with adenosine triphosphate-sensitive potassium channels and nitric oxide. Regulation of adenosine triphosphate-sensitive potassium channels suppresses PC12 cell cytotoxicity induced by amyloid-ß peptide (25-35).

5'-Aza-dC sensitizes paraquat toxic effects on PC12 cell.

Parkinson's disease (PD) is one of the common neurodegenerative diseases that result in the progressive damage of dopaminergic neurons. Environmental exposure, including paraquat, is considered risky for PD. Epigenetics refer to the study of heritable changes in gene expression that occur without a change in DNA sequence. Epigenetic abnormalities (e.g. DNA methylation) have also been found to be causative factors in aging disease, such as PD. How these risk factors cooperate to induce progressive neurodegeneration in PD remains largely unknown. In this study, the PC12 cells was pretreated with methyltransferase inhibitor 5'-aza-2-deoxycytidi(5'-aza-dC) for 24 h, then exposed to paraquat for 12h. The biochemical mechanisms were investigated. The results showed that cell activity remarkably decreased and apoptotic cells increased after paraquat plus 5'-aza-dC treatment. Moreover, compared with paraquat treatment alone, after being exposed to paraquat plus 5'-aza-dC, the level of reactive oxygen species (ROS) increased significantly. The expression of bcl-2 decreased, expressions of bax increased, the rate of bcl-2/bax decreased, and thus expressions of cytochrome C increased. Our findings suggest that 5'-aza-dC modulating DNA methylation could sensitize paraquat toxic effects on PC12 cell by oxidative stress increment and mitochondrial deficit. Demonstration of the interaction of DNA methylation and paraquat provides additional new insights into the pathogenic mechanisms of PD.

[Generation of antitumor response against hepatocellular carcinoma by in vitro transduction of dendritic cells with adeno-associated virus expressing α-fetoprotein].

OBJECTIVE: To investigate the generation of antitumor response against hepatocellular carcinoma by in vitro transduction of dendritic cells (DC) with recombinant adeno-associated virus expressing α-fetoprotein (rAAV-AFP). METHODS: Peripheral blood mononuclear cells were isolated from healthy volunteers. Adherent peripheral blood mononuclear cells were transduced with AAV-AFP and cultured in the presence of granulocyte macrophage colony stimulating factor and interleukin-4 to generate dendritic cells. MTS assay was used to measure the ability of DC transduced with AAV-AFP (AAV-AFP + DC) to stimulate the proliferation of T cell. The phenotype and AFP protein expression of DC and the secretion of IFN (interferon)-γ and IL (interleukin)-4 by T cells were detected by flow cytometry. The killing efficacy of cytotoxic T lymphocytes (CTL) activated by AAV-AFP + DC against AFP positive hepatocellular carcinoma cell lines was detected by lactate dehydrogenase (LDH) release assay. RESULTS: AAV-AFP + DC expressed HLAI (97.12%), HLAII (97.32%), CD80 (38.94%), CD83 (60.84%) and CD86 (98.14%). AFP was secreted by 81.2% of AAV-AFP + DC. And it could stimulate effectively the proliferation of T cell. 19.84% of CD4(+)T cells and 18.65% of CD8(+)T cells activated by AAV-AFP + DC produced IFN-γ but not IL-4 and showed distinct killing activities against AFP positive hepatocellular carcinoma cell lines HepG2 (56.45%) and BEL7402 (78.84%). CONCLUSION: AAV-AFP + DC can elicit distinct antitumor responses against AFP positive hepatocellular carcinoma cell lines so as to provide a basis for further researches on the clinical application of AAV-AFP + DC in the treatment of hepatocellular carcinoma.