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Abstract: Background: Gender is known to be one of the factors linked to differences in cardiovascular morbidity and mortality. However, little information is available regarding gender differences in the risk factors for intracranial cerebral atherosclerosis (ICAS). Objective: This study investigated the risk factors for ICAS separately by gender in an asymptomatic population. Methods: We collected data from a consecutive series of 935 subjects who had no history of stroke and who had undergone transcranial Doppler ultrasonography (TCD). For each subject, their medical history was documented and tests for biochemical markers were performed. Multiple logistic regression analyses were separately conducted to assess the risk factors associated with ICAS by gender. Results: The risk factors for asymptomatic ICAS were determined for every 10-year increase in age (odds ratio [OR] = 1.74, 95% confidence interval [CI] = 1.23–2.46), diabetes mellitus (DM) (OR = 3.45, 95% CI = 1.49–7.95), smoking (OR = 2.09, 95% CI = 1.01–4.32), and hypercholesterolemia (OR = 3.31, 95% CI = 1.15–9.50) for male subjects; risk factors female subjects included hypertension (OR = 2.10, 95% CI = 1.40–3.15) and DM (OR = 2.45, 95% CI = 1.11–5.44). An additional stratified analysis indicated that there was no significant risk factor for male subjects aged <50 years, whereas hypertension (OR = 2.90, 95% CI = 1.57–5.37) was the significant risk factor for female subjects aged <50 years. For male subjects aged ≥50 years, DM (OR = 6.00, 95% CI = 1.87–19.20), hypercholesterolemia (OR = 4.72, 95% CI = 1.05–21.19), and every 10-year increase in age (OR = 4.33, 95% CI = 2.02–9.28) were significant risk factors for asymptomatic ICAS, whereas DM (OR = 2.93, 95% CI = 1.14–7.48) was significant for female subjects aged ≥50 years. Conclusions: The findings suggest that the risk factors for asymptomatic ICAS differ between sexes, indicating a possible role of sex hormones in the development of ICAS. [Copyright &y& Elsevier]

Abstract: In this paper, we consider time-optimal path planning for - gantry systems along circular paths, in which acceleration and jerk limitations of each actuator are taken into full account. The physical limitations are expressed as highly nonlinear state/input constraints, and are mathematically very difficult to handle effectively. In this context, we formulate the time-optimal problem under reasonably simplified constraints and derive its solution in feedback form. Numerical examples demonstrate that the proposed time-optimal circular path planning method decreases the traverse time significantly compared to the well-known s-curve method. [Copyright &y& Elsevier]

Combination treatment consisting of oncolytic adenovirus (Ad) and paclitaxel (PTX) is a promising strategy to achieve synergistic antitumor effect. However, a co-administration approach is subject to inherent limitations due to the poor solubility of PTX and chemoresistance of tumor cells. In order to overcome these limitations, an oncolytic Ad expressing a p53 variant (oAd-vp53) that is resistant to p53 inactivation in the tumor microenvironment was complexed with PEGylated and PTX-conjugated polymeric micelle (APP). This approach generated an oAd-vp53/APP complex (176.4 nm in diameter) that could concurrently deliver both oncolytic Ad and the nanoparticulate drug APP to tumors. APP-complexed replication-incompetent Ad (dAd/APP) exhibited 12-fold higher transduction efficiency than naked dAd in coxsackie adenovirus receptor (CAR)-negative cancer cells. This increased efficiency was attributed to more efficient cellular internalization mediated by charge interactions between APP and anionic cell membranes. Furthermore, oAd-vp53/APP elicited synergistically higher cancer cell killing than naked oAd-vp53, APP, or oAd-vp53 in combination with PTX (oAd-vp53 + PTX); this synergistic effect was shown to be due to superior induction of apoptosis and viral replication. Importantly, oAd-vp53/APP induced more potent and synergistic antitumor effect through both local and systemic administration by enhancing replication of oncolytic Ad and induction of apoptosis in tumor tissue. Further, the APP coating on the surface of Ad markedly attenuated the host immune response against Ad and decreased hepatic sequestration, resulting in minimal hepatotoxicity and a good safety profile. These attributes enabled oAd-vp53/APP to elicit potent antitumor effect over multiple treatment cycles. Altogether, we demonstrate that concurrent delivery of oncolytic Ad and APP as a single nanocomplex is a promising strategy for achieving synergistic antitumor effect. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Dried roots of Polygonum multiflorum have traditionally been used in the retarding of aging process in East Asian countries and its extracts exhibit anti-oxidative activities. Materials and methods: Neuroprotective effects of ethyl acetate extract from Polygonum multiflorum (EEPM) were investigated against glutamate-induced oxidative cell death in HT22 hippocampal cells. Cell viability, cytotoxicity, morphological, flow cytometry, and Western blot assays were performed in order to observe alterations of neuronal cell survival or death related pathways. Results: Pretreatment with EEPM resulted in significantly decreased glutamate-induced neurotoxicity and also resulted in drastically inhibited glutamate-induced apoptotic and necrotic neuronal death. To elucidate possible pathways of neuroprotection by EEPM, we explored the activation of mitogen activated protein kinases (MAPKs), phosphatidylinositol-3-kinase, and cAMP responsive element binding protein (CREB). Treatment with glutamate alone led to activation of extracellular regulated kinase (ERK), Jun N-terminal kinase, and p38 during the late phase after glutamate exposure, but pretreatment with EEPM resulted in significantly attenuated activation of these proteins. Pretreatment with EEPM resulted in increased activation of CREB. The specific inhibitors of ERK and p38, PD98059 and SB203580, abrogated the neuroprotective effects of EEPM. When we evaluated calpain I and striatal-enriched protein tyrosine phosphatase (STEP), active form of calpain I was significantly increased after glutamate exposure, and, along with this, active form of STEP showed a decrease. Pretreatment with EEPM resulted in significant recovery of pro-calpain I and active form of STEP caused by glutamate. Co-treatment with calpain inhibitor ALLN and EEPM had a synergistic effect on neuronal death and contributed to blockade of activation of both ERK and p38 with increased activation of CREB. Conclusions: These results suggest that Polygonum multiflorum extract may have neuroprotective effects through both alleviation of ERK and p38 activation with increased activation of CREB under oxidative stress and has potential as a therapeutic intervention for treatment of oxidative neuronal death. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Uncaria sinensis (US) has been used in traditional Korean medicine to treat vascular disease and to relieve various neurological symptoms. Aim of the study: Scientific evidence related to the effectiveness or action mechanism of US on cerebrovascular disease has not been examined experimentally. Here, we investigated the cerebrovascular protective effect of US extracts on photothrombotic ischemic injury in mice. Materials and methods: US hexane extracts (HEUS), ethyl acetate extracts (EAEUS) and methanol extracts (MEUS) were administered intraperitoneally 30min before ischemic insults. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, neurological score and the activation of Akt and eNOS in ischemic brain. Results: HEUS more significantly reduced infarct volume and edema than did EAEUS and MEUS following photothrombotic cortical occlusion. HEUS produced decreased infarct volume and edema size, and improved neurological function in a concentration-dependent manner (10, 50, and 100mg/kg). However, HEUS did not reduce brain infarction in eNOS KO mice, suggesting that the protective effect of HEUS is primarily endothelium-dependent. Furthermore, HEUS (10–300μg/ml) produced a concentration-dependent relaxation in mouse aorta and rat basilar artery, which was not seen in eNOS KO mouse aorta, suggesting that HEUS cause vasodilation via an eNOS-dependent mechanism. This correlated with increased phosphorylation of Akt and eNOS in the brains of HEUS-treated mice. Conclusion: HEUS prevent cerebral ischemic damage by regulating Akt/eNOS signaling. US, herbal medicine, may be the basis of a novel strategy for the therapy of stroke. [Copyright &y& Elsevier]