Risk of mortality in pediatric intensive care unit, assessed by PRISM-III.

This study aimed at evaluating the mortality rate in a PICU applying PRISM-III. Two hundred and twenty one infants and children consecutively admitted to PICU of Tabriz Children's Hospital were studied during a 13 months period of time. Data required for calculating the PRISM-III score were collected during the first 24 h of PICU stay in all patients.

Thrombospondin-1-CD47 blockade and exogenous nitrite enhance ischemic tissue survival, blood flow and angiogenesis via coupled NO-cGMP pathway activation.

Tissue ischemia and ischemia-reperfusion (I/R) remain sources of cell and tissue death. Inability to restore blood flow and limit reperfusion injury represents a challenge in surgical tissue repair and transplantation. Nitric oxide (NO) is a central regulator of blood flow, reperfusion signaling and angiogenesis.

Dietary nitrate and nitrite modulate blood and organ nitrite and the cellular ischemic stress response.

Dietary nitrate, found in abundance in green vegetables, can be converted to the cytoprotective molecule nitrite by oral bacteria, suggesting that nitrate and nitrite may represent active cardioprotective constituents of the Mediterranean diet. We therefore tested the hypothesis that dietary nitrate and nitrite levels modulate tissue damage and ischemic gene expression in a mouse liver ischemia-reperfusion model. We found that stomach content, plasma, heart, and liver nitrite levels were significantly reduced after dietary nitrate and nitrite depletion and could be restored to normal levels with nitrite supplementation in water.

Autoimmune thyroid disease in children and adolescents with type 1 diabetes mellitus in Northwest Iran.

Objective: To investigate the prevalence of autoimmune thyroid disease in diabetic children in Northwest Iran.

Methods: In a cross-sectional study from February 2006 to November 2007, serum levels of anti-thyroid peroxidase, and anti-thyroglobulin antibodies, and thyrotropin hormone were measured with ELISA method in 176 diabetic children (78 Male and 98 Female) at a mean age of 8.3 +/- 3.

Effects of nitrite on modulating ROS generation following ischemia and reperfusion.

It has long been known that the generation of reactive oxygen species (ROS) is a major cause of injury after ischemia/reperfusion. More recently it has emerged that the predominant source of these ROS are the mitochondria, which are specifically damaged during prolonged ischemic episodes. Several strategies have been tested to attenuate mitochondrial damage and reperfusion ROS.

Nitrite exerts potent negative inotropy in the isolated heart via eNOS-independent nitric oxide generation and cGMP-PKG pathway activation.

The ubiquitous anion nitrite (NO(2)(-)) has recently emerged as an endocrine storage form of nitric oxide (NO) and a signalling molecule that mediates a number of biological responses. Although the role of NO in regulating cardiac function has been investigated in depth, the physiological signalling effects of nitrite on cardiac function have only recently been explored. We now show that remarkably low concentrations of nitrite (1 nM) significantly modulate cardiac contractility in isolated and perfused Langendorff rat heart.

Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function.

Nitrite, once thought to be an inert biomarker of NO formation, is now recognized as an endocrine storage pool of bioactive NO. While nitrite mediates a number of hypoxic responses, one of its most robust effects is its ability to confer cytoprotection after ischemia/reperfusion in a number of organs and models. The mechanism of this cytoprotection appears to be mediated at the level of the mitochondrion.

Nitrite as regulator of hypoxic signaling in mammalian physiology.

In this review we consider the effects of endogenous and pharmacological levels of nitrite under conditions of hypoxia. In humans, the nitrite anion has long been considered as metastable intermediate in the oxidation of nitric oxide radicals to the stable metabolite nitrate. This oxidation cascade was thought to be irreversible under physiological conditions.

Nitrite reductase activity of cytochrome c.

Small increases in physiological nitrite concentrations have now been shown to mediate a number of biological responses, including hypoxic vasodilation, cytoprotection after ischemia/reperfusion, and regulation of gene and protein expression. Thus, while nitrite was until recently believed to be biologically inert, it is now recognized as a potentially important hypoxic signaling molecule and therapeutic agent. Nitrite mediates signaling through its reduction to nitric oxide, via reactions with several heme-containing proteins.

Myocardial protection by nitrite: evidence that this reperfusion therapeutic will not be lost in translation.

The circulating anion nitrite (NO(2)(-)), previously thought to be an inert product of nitric oxide (NO) oxidation, has now been identified as an important storage reservoir of bioavailable NO in the blood and tissues. Reduction of NO(2)(-) to NO over the physiologic pH and oxygen gradient by deoxyhemoglobin, myoglobin, xanthine oxidoreductase, and by nonenzymatic acidic disproportionation has been demonstrated to confer cytoprotection against ischemia-reperfusion injury in the heart, liver, brain, and kidney. Here, we review the mechanisms that have been established to regulate hypoxic NO(2)(-) reduction to NO, analyze the preclinical and clinical evidence supporting NO(2)(-)-mediated cytoprotection after ischemia-reperfusion injury, and examine the therapeutic potential of NO(2)(-) for cardiovascular disease.

Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury.

The nitrite anion is reduced to nitric oxide (NO*) as oxygen tension decreases. Whereas this pathway modulates hypoxic NO* signaling and mitochondrial respiration and limits myocardial infarction in mammalian species, the pathways to nitrite bioactivation remain uncertain. Studies suggest that hemoglobin and myoglobin may subserve a fundamental physiological function as hypoxia dependent nitrite reductases.

Nitrite reductase activity of hemoglobin as a systemic nitric oxide generator mechanism to detoxify plasma hemoglobin produced during hemolysis.

Hemoglobin (Hb) potently inactivates the nitric oxide (NO) radical via a dioxygenation reaction forming nitrate (NO(3)(-)). This inactivation produces endothelial dysfunction during hemolytic conditions and may contribute to the vascular complications of Hb-based blood substitutes. Hb also functions as a nitrite (NO(2)(-)) reductase, converting nitrite into NO as it deoxygenates.

Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction.

Background: Accumulating evidence suggests that the ubiquitous anion nitrite (NO2-) is a physiological signaling molecule, with roles in intravascular endocrine nitric oxide transport, hypoxic vasodilation, signaling, and cytoprotection. Thus, nitrite could enhance the efficacy of reperfusion therapy for acute myocardial infarction. The specific aims of this study were (1) to assess the efficacy of nitrite in reducing necrosis and apoptosis in canine myocardial infarction and (2) to determine the relative role of nitrite versus chemical intermediates, such as S-nitrosothiols.

Copper dependence of the biotin switch assay: modified assay for measuring cellular and blood nitrosated proteins.

Studies have shown that modification of critical cysteine residues in proteins leads to the regulation of protein function. These modifications include disulfide bond formation, glutathionylation, sulfenic and sulfinic acid formation, and S-nitrosation. The biotin switch assay was developed to specifically detect protein S-nitrosation (S.

Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer.

Nitrite (NO(2)(-)) is an intrinsic signaling molecule that is reduced to NO during ischemia and limits apoptosis and cytotoxicity at reperfusion in the mammalian heart, liver, and brain. Although the mechanism of nitrite-mediated cytoprotection is unknown, NO is a mediator of the ischemic preconditioning cell-survival program. Analogous to the temporally distinct acute and delayed ischemic preconditioning cytoprotective phenotypes, we report that both acute and delayed (24 h before ischemia) exposure to physiological concentrations of nitrite, given both systemically or orally, potently limits cardiac and hepatic reperfusion injury.

Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics.

The anion nitrite (NO(2)(-)) constitutes a biochemical reservoir for nitric oxide (NO). Nitrite reduction to NO may be catalyzed by hemoglobin, myoglobin or other metal-containing enzymes and occurs at increasing rates under conditions of physiologic hypoxia or ischemia. A number of laboratories have now demonstrated in animal models the ability of nitrite to provide potent cytoprotection following focal ischemia-reperfusion (IR) injury of the heart, liver, brain, and kidney.

Endothelial progenitor cell mobilization and increased intravascular nitric oxide in patients undergoing cardiac rehabilitation.

Purpose: We investigated whether cardiac rehabilitation participation increases circulating endothelial progenitor cells (EPCs) and benefits vasculature in patients already on stable therapy previously shown to augment EPCs and improve endothelial function.

Methods: Forty-six of 50 patients with coronary artery disease completed a 36-session cardiac rehabilitation program: 45 were treated with HMG-CoA reductase inhibitor (statin) therapy > or = 1 month (average baseline low-density lipoprotein cholesterol = 81 mg/dL). Mononuclear cells isolated from blood were quantified for EPCs by flow cytometry (CD133/VEGFR-2 cells) and assayed in culture for EPC colony-forming units (CFUs).

Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin.

Increased platelet activation is recognized in patients with sickle cell disease (SCD), but its pathogenesis and clinical relevance remain uncertain. Pulmonary arterial hypertension (PAH), an important complication of SCD, is characterized by a proliferative pulmonary vasculopathy, in situ thrombosis, and vascular dysfunction related to scavenging of nitric oxide (NO) by hemoglobin released into blood plasma during intravascular hemolysis. We investigated links between platelet activation, PAH and NO scavenging in patients with SCD.

Concerted nitric oxide formation and release from the simultaneous reactions of nitrite with deoxy- and oxyhemoglobin.

Recent studies reveal a novel role for hemoglobin as an allosterically regulated nitrite reductase that may mediate nitric oxide (NO)-dependent signaling along the physiological oxygen gradient. Nitrite reacts with deoxyhemoglobin in an allosteric reaction that generates NO and oxidizes deoxyhemoglobin to methemoglobin. NO then reacts at a nearly diffusion-limited rate with deoxyhemoglobin to form iron-nitrosyl-hemoglobin, which to date has been considered a highly stable adduct and, thus, not a source of bioavailable NO.

Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration.

Previous studies have revealed a novel interaction between deoxyhemoglobin and nitrite to generate nitric oxide (NO) in blood. It has been proposed that nitrite acts as an endocrine reservoir of NO and contributes to hypoxic vasodilation and signaling. Here, we characterize the nitrite reductase activity of deoxymyoglobin, which reduces nitrite approximately 36 times faster than deoxyhemoglobin because of its lower heme redox potential.

Measurement of circulating nitrite and S-nitrosothiols by reductive chemiluminescence.

Considerable disparities in the reported levels of basal human nitrite and S-nitrosothiols (RSNO) in blood have brought methods of quantifying these nitric oxide (NO) metabolites to the forefront of NO biology. Ozone-based chemiluminescence is commonly used and is a robust method for measuring these species when combined with proper reductive chemistry. The goal of this article is to review existing methodologies for the measurement of nitrite and RSNO by reductive chemiluminescence.

Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasis.

Nitrite represents a bioactive reservoir of nitric oxide (NO) that may modulate vasodilation, respiration and cytoprotection after ischemia-reperfusion injury. Although nitrite formation is thought to occur via reaction of NO with oxygen, this third-order reaction cannot compete kinetically with the reaction of NO with hemoglobin to form nitrate. Indeed, the formation of nitrite from NO in the blood is limited when plasma is substituted with physiological buffers, which suggests that plasma contains metal-based enzymatic pathways for nitrite synthesis.