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Sender's message: Sepsis or genomics or altitude: JKB_daily1

Sent on Friday, 2010 Apr 02
Search (sepsis[MeSH Terms] OR septic shock[MeSH Terms] OR altitude[MeSH Terms] OR genomics[MeSH Terms] OR genetics[MeSH Terms] OR retrotransposons[MeSH Terms] OR macrophage[MeSH Terms]) AND ("2009/8/8"[Publication Date] : "3000"[Publication Date]) AND (("Science"[Journal] OR "Nature"[Journal] OR "The New England journal of medicine"[Journal] OR "Lancet"[Journal] OR "Nature genetics"[Journal] OR "Nature medicine"[Journal]) OR (Hume DA[Author] OR Baillie JK[Author] OR Faulkner, Geoffrey J[Author]))
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1.	Nat Med. 2010 Mar;16(3):279-85. Epub 2010 Feb 28. Kynurenine is an endothelium-derived relaxing factor produced during inflammation. Wang Y, Liu H, McKenzie G, Witting PK, Stasch JP, Hahn M, Changsirivathanathamrong D, Wu BJ, Ball HJ, Thomas SR, Kapoor V, Celermajer DS, Mellor AL, Keaney JF Jr, Hunt NH, Stocker R. Centre for Vascular Research, School of Medical Sciences (Pathology) and Bosch Institute, Faculty of Medicine, University of Sydney, Sydney, Australia. Comment in: Nat Med. 2010 Mar;16(3):265-7. Control of blood vessel tone is central to vascular homeostasis. Here we show that metabolism of tryptophan to kynurenine by indoleamine 2,3-dioxygenase (Ido) expressed in endothelial cells contributes to arterial vessel relaxation and the control of blood pressure. Infection of mice with malarial parasites (Plasmodium berghei) or induction of endotoxemia in mice led to endothelial expression of Ido, decreased plasma tryptophan concentration, increased kynurenine concentration and hypotension. Pharmacological inhibition of Ido increased blood pressure in systemically inflamed mice but not in mice deficient in Ido or interferon-gamma, which is required for Ido induction. Both tryptophan and kynurenine dilated preconstricted porcine coronary arteries; the dilating effect of tryptophan required the presence of active Ido and an intact endothelium, whereas the effect of kynurenine was endothelium independent. The arterial relaxation induced by kynurenine was mediated by activation of the adenylate and soluble guanylate cyclase pathways. Kynurenine administration decreased blood pressure in a dose-dependent manner in spontaneously hypertensive rats. Our results identify tryptophan metabolism by Ido as a new pathway contributing to the regulation of vascular tone.
	PMID: 20190767 [PubMed - indexed for MEDLINE]
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	Publication Types: Research Support, Non-U.S. Gov't MeSH Terms: Adenylate Cyclase/metabolism Animals Blood Pressure/drug effects Blood Pressure/physiology Coronary Vessels/drug effects Coronary Vessels/physiopathology Dose-Response Relationship, Drug Endothelium, Vascular/enzymology Endothelium, Vascular/physiology Endothelium, Vascular/physiopathology Endothelium-Dependent Relaxing Factors/physiology* Endotoxemia/physiopathology Enzyme Activation/physiology Guanylate Cyclase/metabolism Guanylate Cyclase/physiology Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism Indoleamine-Pyrrole 2,3,-Dioxygenase/physiology Inflammation/physiopathology* Interferon-gamma/physiology Kynurenine/biosynthesis Kynurenine/pharmacology Kynurenine/physiology* Malaria/physiopathology Mice Mice, Inbred C57BL Muscle, Smooth, Vascular/drug effects Muscle, Smooth, Vascular/physiology Plasmodium berghei Rats Rats, Inbred SHR Tryptophan/blood Tryptophan/pharmacology Tryptophan/physiology Substances: Endothelium-Dependent Relaxing Factors Kynurenine Tryptophan Interferon-gamma Indoleamine-Pyrrole 2,3,-Dioxygenase Adenylate Cyclase Guanylate Cyclase

2.	Nat Med. 2010 Mar;16(3):334-8. Epub 2010 Jan 28. A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Akahata W, Yang ZY, Andersen H, Sun S, Holdaway HA, Kong WP, Lewis MG, Higgs S, Rossmann MG, Rao S, Nabel GJ. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA. Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe and Asia since this alphavirus reemerged from Kenya in 2004. The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. Here, we describe a new vaccine that protects against CHIKV infection of nonhuman primates. We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from alternative CHIKV strains. Monkeys immunized with VLPs produced high-titer neutralizing antibodies that protected against viremia after high-dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, indicating a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans. PMCID: PMC2834826 [Available on 2010/9/1]
	PMID: 20111039 [PubMed - indexed for MEDLINE]
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	Publication Types: Research Support, N.I.H., Extramural MeSH Terms: Alphavirus Infections/immunology Alphavirus Infections/prevention & control* Animals Antibodies, Viral/immunology Antibody Formation/immunology Cells, Cultured Chikungunya virus/immunology* Female Humans Immunoglobulin G/immunology Macaca mulatta/immunology Macaca mulatta/virology Mice Mice, Inbred BALB C Viral Envelope Proteins/immunology Viral Vaccines/immunology Viral Vaccines/therapeutic use* Viremia/immunology Viremia/prevention & control Substances: Antibodies, Viral Immunoglobulin G Viral Envelope Proteins Viral Vaccines