Recently green tea, which is the traditional drink of Japan and China, has been recognized as healthful. Catechins, which are polyphenol chemical compounds found in abundance in green tea, possess physiological effects including antioxidative and bactericidal action as well as antitumor activity. Four main catechins are contained within green tea: epicatechin (EC), epicatechin gallate (ECg), epigallocatechin (EGC) and epigallocatechin gallate (EGCg). These catechins display strong antioxidant activity, 1) which efficiently eliminates reactive oxygen species. The antioxidant mechanism is believed to involve radical elimination by the phenolic hydroxyl group of the catechin structure.2) EGCg and EGC in catechin have demonstrated anti-tumor growth and a strong apoptosis induction effect in the human lung tumor cells H661 and H1299 and the induction was inhibited by catalase.3) This paper indicates that hydrogen peroxide participated in the apoptotic action of EGCg; however, the chemical mechanism has not been clarified.On the other hand, we noted previously that catechins exhibit a wide antibacterial spectrum of gram-negative bacteria and positive fungus in terms of germicidal action.4) The structure-activity relationship of catechin and bactericidal activity occurs in the following order: ECgϾEGCgϾEGCϾ EC.5) Furthermore, the gallate and pyrogallol moieties are necessary with respect to this activity. Investigation of EGCg uptake of liposomal membranes 6) and ultra-structure change on sterilization of trychophyton employing electron microscopy reveals that the action is based on the membrane injury action of bacterial cells. 7) Moreover, it has been reported that the bactericidal effect of EGCg is stronger for gram-positive bacteria than for gram-negative bacteria due to the difference in the amount of EGCg absorbed by the bacterial cell. EGCg was thought to carry a net negative charge in aqueous solution (pH 6-7); furthermore, it was believed to bind to the membrane component of bacteria as a result of electrostatic interaction, which led to membrane damage. 8)However, chemical elucidation of the mechanism via which EGCg causes membrane injury following binding to the liposome remains unclear. We previously established a highly sensitive analytical method for catechin using peroxalate chemiluminescent reaction.9) The principle is based on the reaction mechanism in which catechin reacts with dissolved oxygen in basic solution, resulting in the generation of active oxygen. In this study, we established that the reactive oxygen produced by catechin was hydrogen peroxide via chemiluminescent methodology and electron spin resonance (ESR) using a spin-trapping method. We believed that the hydrogen peroxide generation ability of EGCg was a central component with respect to bactericidal activity; consequently, examination was conducted in detail regarding the role of hydrogen peroxide-mediated bactericidal activity of EGCg and the effect of bactericidal activity of EGCg and hydrogen peroxide in terms of gram-negative (9 o...

Background and Purpose-The natural history of unruptured intracranial aneurysms remains unclear, and management strategy is not well defined. Methods-From January 2003 to December 2012, we enrolled patients with aneurysm in our institution. In total, 2252 patients with 2897 aneurysms were eligible for analysis, and 1960 eligible aneurysms were conservatively managed. Precise 3-dimensional evaluation was conducted using computed tomography angiography, digital subtraction angiography, or magnetic resonance angiography. We then assessed the risk of aneurysm rupture, mortality, and morbidity associated with aneurysm characteristics, demographics, and known health/lifestyle risk factors. Results-The mean follow-up duration was 7388 aneurysm-years. During observation, 56 aneurysms ruptured, resulting in an overall rupture rate per year of 0.76% (95% confidence interval, 0.58-0.98). The mean initial visit to rupture interval was 547 days. Aneurysm size, location, daughter sac, and history of subarachnoid hemorrhage were significant independent predictors for aneurysm rupture. Aneurysms that were ≥5 mm were associated with a significantly increased risk of rupture when compared with 2-to 4-mm aneurysms (unadjusted hazard ratio, 12.24; 95% confidence interval, 7.15-20.93). Of 56 patients who experienced hemorrhage, 29 (52 %) died or were rendered severely disabled. Of the patients who had large or giant aneurysms, none recovered without deficits, and the mortality rate after rupture was 69%. For aneurysms sized <5 mm, the mortality rate was 18%. Conclusions-Larger

Backgrounds and Purpose-The authors evaluated the incidence of rupture of unruptured intracranial saccular aneurysm during observation. Methods-Between January 2003 and December 2006, a total of 419 patients with 529 unruptured intracranial saccular aneurysms were observed without treatment. The mean follow-up duration was 905.3 days. Aneurysm size was measured by 3-dimensional CT angiography. Clinical and 3-dimensional CT angiography follow-up were obtained every 6 months. Results-Nineteen aneurysms ruptured during observation resulting in a 1.4% rupture rate per year. A history of subarachnoid hemorrhage (hazard ratio, 7.3; 95% CI, 2.5 to 21.2), posterior circulation aneurysm (hazard ratio, 2.9; 95% CI, 1.1 to 8), and large size were significant independent predictors for aneurysm rupture. Conclusions Clinical Materials and MethodsFrom January 2003 through December 2006, a total of 419 patients with 529 UIAs were referred to our institution. Patient information and clinical presentation is summarized in Table 1.Size of the UIAs was measured by 3-dimensional CT angiography (Sensation16, Siemens, Germany). Based on the findings of 3-dimensional CT angiography, all UIAs were classified into the following categories: small (S; 0 to 4.9 mm in diameter), medium/ small (MS; 5 to 9.9 mm in diameter with small neck (0 to 3.9 mm), medium/wide (MW; 5 to 9.9 mm in diameter) with a wide neck (Ͼ4 mm), large (L; Ͼ10 mm), and giant (G; Ͼ25 mm). These aneurysms were followed by 3-dimensional CT angiography every 6 months.Data were analyzed using the biomedical data package statistical program (Version 7.0; BMDP Statistical Software, Inc, University of California, Los Angeles, Calif). Categorical variables were compared using the Fisher exact 2-tailed test, the Pearson 2 test, or the test for determining linear trend. Continuous variables were compared among groups by using the Mann-Whitney U test or the Student t test. For life-table analysis and Cox proportional hazards regression model, each patient was followed to the time of subarachnoid hemorrhage (SAH), death due to causes other than SAH, or to the last possible follow-up contact. The average annual incidence of SAH was calculated by determining the number of first-event SAH divided by the number of person-years of follow-up. Cumulative rates of SAH were estimated using the Kaplan-Meier product-limit method. ResultsNineteen aneurysms ruptured during the follow-up period. The annual incidence of SAH was 1.4% during observation. Incidence of rupture was strongly correlated with aneurysm size. The annual rupture rate by size classification was 0.8% (S), 1.2% (M), 7.1% (L), and 43.1% (G), respectively. Details of ruptured aneurysms under conservative observation are summarized in Table 2.In patients with a history of SAH, the hazard ratio (HR) was 7.3 (95% CI, 2.5 to 21.2, PϽ0.001). Particularly in S-sized UIAs, 2 of 8 (25%) were associated with a history of SAH. The risk of rupture in S-sized UIAs with a history of SAH was 5.5 (95% CI, 0.9 to 32.4) compared with patients ...

Arakawa H, Chitravanshi VC, Sapru HN. The hypothalamic arcuate nucleus: a new site of cardiovascular action of angiotensin-(1-12) and angiotensin II. Am J Physiol Heart Circ Physiol 300: H951-H960, 2011. First published December 24, 2010 doi:10.1152/ajpheart.01144.2010.-The hypothalamic arcuate nucleus (ARCN) has been reported to play a significant role in cardiovascular regulation. It has been hypothesized that the ARCN may be one of the sites of cardiovascular actions of angiotensins (ANGs). Experiments were carried out in urethaneanesthetized, artificially ventilated, adult male Wistar rats. The ARCN was identified by microinjections of N-methyl-D-aspartic acid (NMDA; 10 mM). Microinjections (50 nl) of ANG-(1-12) (1 mM) into the ARCN elicited increases in mean arterial pressure (MAP), heart rate (HR), and greater splanchnic nerve activity (GSNA). The tachycardic responses to ANG-(1-12) were attenuated by bilateral vagotomy. The cardiovascular responses elicited by ANG-(1-12) were attenuated by microinjections of ANG II type 1 receptor (AT1R) antagonists but not ANG type 2 receptor (AT2R) antagonist. Combined inhibition of ANG-converting enzyme (ACE) and chymase in the ARCN abolished ANG-(1-12)-induced responses. Microinjections of ANG II (1 mM) into the ARCN also increased MAP and HR. Inhibition of ARCN by microinjections of muscimol (1 mM) attenuated the pressor and tachycardic responses to intravenously administered ANG-(1-12) and ANG II (300 pmol/kg each). These results indicated that 1) microinjections of ANG-(1-12) into the ARCN elicited increases in MAP, HR, and GSNA; 2) HR responses were mediated via both sympathetic and vagus nerves; 3) AT1Rs, but not AT2Rs, in the ARCN mediated ANG-(1-12)-induced responses; 4) both ACE and chymase were needed to convert ANG-(1-12) to ANG II in the ARCN; and 5) ARCN plays a role in mediating the cardiovascular responses to circulating ANGs. blood pressure; heart rate; microinjection; N-methyl-D-aspartic acid; sympathetic nerve activity THE HYPOTHALAMIC ARCUATE NUCLEUS (ARCN) may play a significant role in cardiovascular regulation (10, 38). Consistent with this notion, we (31) have recently reported that chemical stimulation of the ARCN elicited increases in mean arterial pressure (MAP), heart rate (HR), and sympathetic nerve activity (SNA). These reports have provided a basis for investigations on different neurotransmitters and neuromodulators in the ARCN that may play a role in the regulation of cardiovascular function in normal and pathological states.A new endogenous angiotensin (ANG), ANG-(1-12), has recently been identified (30,44). Intravenous administration of this peptide has been reported to elicit an immediate pressor response in the rat, and this effect was blocked by prior administration of an ANG-converting enzyme (ACE) inhibitor or an ANG II type 1 receptor (AT 1 R) antagonist (30). These data indicated that in the periphery, ANG-(1-12) exerts its actions via a rapid conversion to ANG II (30). High concentrations of ANG-(1-12) have been reported in th...

A combined endovascular and surgical approach conducted in a hybrid OR provides a new strategy for the treatment of complex neurovascular diseases.

BACKGROUND AND PURPOSE:The natural history and therapeutic management of dissecting vertebrobasilar aneurysms without ischemic or hemorrhagic stroke (nonstroke dissecting vertebrobasilar aneurysms) are not well-established. We conservatively followed patients with nonstroke dissecting vertebrobasilar aneurysms and evaluated the factors related to clinical and morphologic deterioration.

This newly developed robotic DSA system provides safe and precise treatment in the fields of endovascular treatment and neurosurgery.

Background-Platelet-activating factor (PAF) and PAF-like phospholipids are inactivated by PAF-acetylhydrolase (PAF-AH).Using nonhyperlipidemic animals, we tested whether local expression of PAF-AH into injured arteries might induce antithrombotic and antiinflammatory effects. Method and Results-Balloon-injured rabbit carotid arteries were infected at the time of injury with an adenovirus expressing either human plasma PAF-AH (AdPAF-AH) or bacterial ␤-galactosidase (AdLacZ) or infused with saline. Seven days later, shear stress-induced thrombosis was observed in all AdLacZ-infected and saline-infused arteries (controls) but eliminated in AdPAF-AH-treated contralateral arteries, even in the presence of epinephrine or an inhibitor of NO production. Injury-induced expression of tissue factor was also significantly suppressed. In AdPAF-AH-treated arteries compared with controls, the expressions of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and macrophage infiltration were decreased by 66%, 66%, and 71%, respectively (PϽ0.01), and intimal area and intima/media ratio were decreased on day 21 by 43% and 52%, respectively (PϽ0.05). Within 1 week after injury, oxidized lipoproteins (OxLDL) had readily accumulated in the arterial wall. However, this was markedly reduced in the AdPAF-AH-treated arteries. No differences in the titers of autoantibodies to OxLDL or total cholesterol in blood were found between controls and AdPAF-AH-treated rabbits. Conclusions-Our results show for the first time that OxLDL accumulates in arteries in nonhyperlipidemic animals within 1 week after injury and that local expression of PAF-AH reduces this accumulation and exerts antiinflammatory, antithrombotic, and antiproliferative effects without changing the plasma levels of PAF-AH activity or titers of autoantibodies to OxLDL. (Circulation. 2005;111:3302-3309.)