Background: The presence of high-density starry dots around the intracerebral hemorrhage (ICH), which we termed as a satellite sign, is occasionally observed in CT. The relationship between ICH with a satellite sign and its functional outcome has not been identified. This study aimed to determine whether the presence of a satellite sign could be an independent prognostic factor for patients with ICH. Methods: Patients with acute spontaneous ICH were retrospectively identified and their initial CT scans were reviewed. A satellite sign was defined as scattered high-density lesions completely separate from the main hemorrhage in at least the single axial slice. Functional outcome was evaluated using the modified Rankin Scale (mRS) at discharge. Poor functional outcome was defined as mRS scores of 3-6. Univariate and multivariate logistic regression analyses were applied to assess the presence of a satellite sign and its association with poor functional outcome. Results: A total of 241 patients with ICH were enrolled in the study. Of these, 98 (40.7%) had a satellite sign. Patients with a satellite sign had a significantly higher rate of poor functional outcome (95.9%) than those without a satellite sign (55.9%, p < 0.0001). Multivariate logistic regression analysis revealed that higher age (OR 1.06; 95% CI 1.03-1.10; p = 0.00016), large hemorrhage size (OR 1.06; 95% CI 1.03-1.11; p = 0.00015), and ICH with a satellite sign (OR 13.5; 95% CI 4.42-53.4; p < 0.0001) were significantly related to poor outcome. A satellite sign was significantly related with higher systolic blood pressure (p = 0.0014), higher diastolic blood pressure (p = 0.0117), shorter activated partial thromboplastin time (p = 0.0427), higher rate of intraventricular bleeding (p < 0.0001), and larger main hemorrhage (p < 0.0001). Conclusions: The presence of a satellite sign in the initial CT scan is associated with a significantly worse functional outcome in ICH patients.

Edited by Miguel De la RosaKeywords: Malaria Apicoplast Heme degradation Ferredoxin Heme oxygenase Double-barreled enzyme a b s t r a c tThe metabolic pathways in apicoplasts of human malaria parasites are promising drug targets. The apicomplexan parasites exhibit delayed cell death when their apicoplast is impaired, but the metabolic pathways within apicoplasts are poorly understood. A nuclear-encoded heme oxygenase (HO)-like protein with an apicoplast-targeted bipartite transit peptide was identified in the Plasmodium falciparum genome. Purified mature recombinant PfHO protein converted heme into bilirubin IXa as confirmed by high-performance liquid chromatography. In addition, PfHO required an iron chelator such as deferoxamine for complete activity. These observations lead to the conclusion that a novel enzymatic heme degradation system is present in human malaria parasites.

(E)-4-Hydroxy-3-methylbut-2-enyl diphosphate synthase (GcpE), which catalyzes the conversion of 2-Cmethyl-D-erythritol cyclodiphosphate (MEcPP) into (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP), is an essential enzyme of the non-mevalonate (2-C-methyl-D-erythritol-4-phosphate (MEP)) pathway for isoprenoid biosynthesis. The terminal steps of the MEP pathway are still not fully understood, although this pathway is necessary for survival in various organisms such as cyanobacteria, plastids of algae and higher plants, and the apicoplast of human malaria parasites. To determine the efficient redox partner for thermophilic cyanobacterial GcpE, We have expressed the gcpE and petF genes in Escherichia coli and studied the protein-protein interaction of GcpE protein with ferredoxin I (PetF) from the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1. Recombinant GcpE protein was purified by an N-terminal His 6 tag and reconstituted as a [4Fe-4S] 2؉ metalloprotein. GcpE was shown to interact strongly with PetF via the bacterial two-hybrid system designed to detect protein-protein interactions. Moreover, a direct protein-protein interaction between PetF and GcpE was confirmed in an in vitro glutathione Stransferase (GST) pull-down assay. To investigate electron transfer activity from PetF to GcpE, we also constructed a NADPH-dependent reducing shuttle system with purified recombinant ferredoxin-NADP ؉ oxidoreductase (PetH) and PetF. The result demonstrated that PetF has the ability to transfer electrons to GcpE. Thus, the combined data provide the first evidence that GcpE is a ferredoxin-dependent enzyme in T. elongatus BP-1.

Edited by Richard Cogdell Keywords:Phycobilin biosynthesis Ferredoxin-dependent enzyme Heme oxygenase Phycocyanobilin:ferredoxin oxidoreductase 1:2 Complex Gel mobility shift assay a b s t r a c tThe HO1 and PcyA genes, encoding heme oxygenase-1 (HO1) and phycocyanobilin (PCB):ferredoxin (Fd) oxidoreductase (PcyA), respectively, are required for chromophore synthesis in photosynthetic light-harvesting complexes, photoreceptors, and circadian clocks. In the PCB biosynthetic pathway, heme first undergoes cleavage to form biliverdin. I confirmed that Fd1 induced the formation of a stable and functional HO1 complex by the gel mobility shift assay. Furthermore, analysis by a chemical cross-linking technique designed to detect protein-protein interactions revealed that HO1 and PcyA directly interact with Fd in a 1:2 ratio. Thus, Fd1, a one-electron carrier protein in photosynthesis, drives the phycobilin biosynthetic pathway.

Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.

Plasma hyaluronan-binding protein (PHBP), a serine protease that can activate coagulation factor VII and prourokinase, circulates in a single-chain form (pro-PHBP) and autoproteolytically converts to an active twochain form with the aid of an effector such as spermidine and heparin. It has been postulated that PHBP plays roles in regulating inflammation, vascular function, fibrosis and atherosclerosis. From the comprehensive screening of natural sources for inhibitors of spermidine-induced pro-PHBP autoactivation, we identified several compounds with a polyphenol feature. Of these inhibitors, tannic acid (IC 50 ‫020.0؍‬ m mM), delphinidin (IC 50 ‫970.0؍‬ m mM), hamamelitannin (IC 50 ‫91.0؍‬ m mM), (؊)-epicatechin gallate (IC 50 ‫42.0؍‬ m mM), and 3,5-di-O-caffeoylquinic acid (IC 50 ‫0.1؍‬ m mM) were potent and selective, and did not inhibit heparin-induced pro-PHBP autoactivation and the active form of PHBP at concentrations 100 times higher than the respective IC 50 values. From evaluation of the activities of related compounds, it has been suggested that a compound with multiple aromatic rings with plural phenolic hydroxyl substituents exhibits potent activity. The inhibitory actions of delphinidin, hamamelitannin, (؊)-epicatechin gallate and 3,5-di-O-caffeoylquinic acid were attenuated by catechol, a minimum polyphenol unit. Thus, it is likely that pro-PHBP binds these potent inhibitors through its site(s) that recognize a catechollike structure. Our results would facilitate understanding of the molecular mechanism of pro-PHBP autoactivation and rational design of a compound for suppressing unregulated pro-PHBP activation.

Background-Migration, proliferation, and matrix-degrading protease expression of smooth muscle cells (SMCs) are major features of intimal hyperplasia after vascular injury. Although MEK kinase 1 (MEKK1) has been shown to regulate cell migration and urokinase plasminogen activator (uPA) expression, the precise role of MEKK1 in this process remains unknown. Methods and Results-We triggered a vascular remodeling model by complete ligation of the right common carotid artery in wild-type (WT) and MEKK1-null (MEKK1 Ϫ/Ϫ ) mice. The intimal areas 28 days after ligation were significantly decreased in the ligated MEKK1 Ϫ/Ϫ arteries compared with WT arteries (28Ϯ8 versus 65Ϯ17 m 2 , PϽ0.05). There were no differences in the ratios of proliferating cell nuclear antigen (PCNA)-positive cells to total cells within the arterial wall between WT and MEKK1 Ϫ/Ϫ arteries. Proliferation capacity also did not differ between WT and MEKK1

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