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PubMed2005

Circulating fragmented nucleosomal DNA and caspase-3 mRNA in patients with lymphoma and myeloma.

Elevated amounts of cell-free nucleic acids are detected in the circulation of cancer patients. The type and pattern of these may vary depending on the origin. Recently, we described the presence of circulating fragmented nucleosomal DNA. In the present study, our aim was to investigate the association between nucleosomal DNA, caspase-3 expression and circulating caspase-3 mRNA, the primary activator of nucleosomal DNA fragmentation. DNA fragmentation was analyzed by gel electrophoresis, and caspase-3 was analyzed by RT-PCR. Plasma samples from 65% of patients were positive for nucleosomal DNA fragmentation, whereas none of the healthy controls showed DNA fragmentation (P = 0.0004). Expression of caspase-3 differed significantly between the cases and controls (P < 0.0001). However, we observed no direct correlation between nucleosomal DNA fragmentation and caspase-3 expression in lymphocytes (P = 0.145). Circulating plasma caspase-3 mRNA was detected by nested RT-PCR, and no significant difference was observed between the patients and the control group (P = 0.5). Our results indicate that caspase-3 expression is increased in lymphocytes from patients. When compared to healthy individuals, no differences were observed in the amount of circulating mRNA. These findings suggest that nucleosomal DNA fragmentation is not correlated with elevated levels of apoptosis and circulating caspase-3 mRNA in circulating tumor cells.

Adult↗
PubMed1988

Circulating immune complex, endotoxin, and biliary infection in patients with biliary obstruction.

Immunoglobulin A-containing circulating immune complexes, immunoglobulin G-containing circulating immune complexes, and endotoxin were measured in the sera of patients with obstructive jaundice. The bile of patients with percutaneous transhepatic biliary drainage was also cultured for bacteriologic studies. There was a significantly positive correlation between the endotoxin levels and both immunoglobulin A-containing circulating immune complex and immunoglobulin G-containing circulating immune complex. The endotoxin levels of the patients with gram-negative infections were significantly increased compared with those of the patients with sterile cultures. The immunoglobulin G-containing circulating immune complex levels of the patients with bacteria in bile were significantly increased compared with those of the patients with sterile cultures. The immunoglobulin A-containing circulating immune complex levels of the patients with bacteria in bile were slightly increased, but the difference did not reach statistical significance. These results indicate that one of the causes of increased circulating immune complex levels may be endotoxemia in combination with biliary infection in patients with biliary obstruction.

Antigen-Antibody Complex↗
PubMed1995

The 1994 Von Sallman Lecture. The optic nerve head circulation in health and disease.

This is a brief overview of multifaceted anatomical, experimental and clinical studies conducted by the author since 1955 on the optic nerve head circulation in health and disease. Conclusions, based on the accumulated information provided by these studies, are summarized. The studies on the pattern of blood supply of the optic nerve head have shown that: (a) its main source of blood supply is the posterior ciliary artery circulation, with retinal circulation supplying only the surface nerve fiber layer, (b) there is marked interindividual variation in the blood supply pattern, and (c) the blood supply in the optic nerve head has a sectorial distribution. The various factors which produce interindividual variation in the blood supply of the optic nerve head are discussed, particularly those in the posterior ciliary artery circulation; this is because all available evidence indicates that it is derangement in the posterior ciliary circulation in the optic nerve head that is primarily responsible for the common ischemic disorders of the optic nerve head, e.g. anterior ischemic optic neuropathy and glaucomatous optic neuropathy. Factors that may derange the blood flow in the optic nerve head include defective autoregulation of blood flow in it, vascular changes in its feeding arteries, hematologic abnormalities, systemic arterial hypertension and hypotension, and intraocular pressure; their roles are discussed. For better understanding and management of optic nerve head ischemic disorders, there is an urgent need for an accurate clinical method of assessment of blood flow in the posterior ciliary circulation in optic nerve head, since no satisfactory method is currently available. Redness or pallor of the optic disk on ophthalmoscopy is not a true guide to the optic nerve head vascularity as it gives no information about the state of the posterior ciliary circulation. Fluorescein fundus angiography, though far superior to the optic disk color for evaluation of optic nerve head vascularity, has a number of limitations. All these topics and various controversies about them are discussed briefly.

Animals↗
PubMed2000

Increased circulating calcitonin in cirrhosis. Relation to severity of disease and calcitonin gene-related peptide.

Increased circulating levels of the neuropeptide calcitonin gene-related peptide (CGRP) have recently been described in cirrhosis. CGRP is formed by alternative transcription of the calcitonin/alpha-CGRP gene, which also gives rise to calcitonin (CT). This study was undertaken to determine circulating plasma concentrations of CT in patients with cirrhosis in relation to the severity of disease and the plasma level of CGRP. Moreover, the kinetics of CT was evaluated for different organ systems by determination of arteriovenous extraction. Thirty-nine patients with cirrhosis (Child-Turcotte classes A/B/C, n = 10/22/7) were studied under a hemodynamic investigation and compared with 13 control subjects without liver disease. CT and CGRP in arterial and organ venous plasma were determined by radioimmunoassays. In patients with cirrhosis, circulating CT was significantly increased versus control (12.1 v 6.9 pmol/L, P < .001) and a direct relation to the Child-Turcotte score was found (P < .005). The increased circulating CT was directly correlated with increased CGRP (r = .29, P < .05). No significant arteriovenous extraction of circulating CT was observed in the kidneys, hepatosplanchnic system, lower extremities, or peripheral circulation, but there was a substantial rate of pulmonary disposal and clearance (P < .005). It is concluded that in addition to thyroid production, increased circulating CT in cirrhosis is most likely due to overexpression of the calcitonin/alpha-CGRP gene, with relation to the severity of disease and possibly to an accompanying pulmonary dysfunction.

Adult↗
PubMed1996

Increased circulating intercellular adhesion molecule-1 levels in type II diabetic patients: the possible role of metabolic control and oxidative stress.

Blood levels of the circulating form of the integrin intercellular adhesion molecule-1 (ICAM-1), malondialdehyde (MDA), and hemoglobin A1c (HbA1c) were studied at baseline and 3 months after improved metabolic control in 25 type II diabetic patients without signs of macroangiopathy, and were compared with those in 15 matched healthy normal controls. Circulating ICAM-1 and MDA levels were increased in diabetic patients, both at baseline and 3 months later. However, with improving metabolic control HbA1c, circulating ICAM-1, and MDA significantly decreased. A significant correlation between circulating ICAM-1, HbA1c, and MDA was found in diabetic patients at each time. Multiple regression analysis considering circulating ICAM-1 as the dependent variable and HbA1c and MDA as independent variables, showed a significant correlation between the three variable at each time. Similar correlations were found in control subjects. These data show increased levels of circulating ICAM-1 in type II diabetic patients, independent of the presence of macroangiopathy. Moreover, these results suggest that oxidative stress and metabolic control might participate in determining increased circulating ICAM-1 levels in both type II diabetic patients and normal subjects.

Diabetes Mellitus, Type 2↗
PubMedDate not supplied

Seasonal variation of Titan's atmospheric structure simulated by a general circulation model.

The seasonal variation of Titan's atmospheric structure with emphasis on the stratosphere is simulated by a three-dimensional general circulation model. The model includes the transport of haze particles by the circulation. The likely pattern of meridional circulation is reconstructed by a comparison of simulated and observed haze and temperature distribution. The GCM produces a weak zonal circulation with a small latitudinal temperature gradient, in conflict with observation. The direct reason is found to be the excessive meridional circulation. Under uniformly distributed opacity sources, the model predicts a pair of symmetric Hadley cells near the equinox and a single global cell with the rising branch in the summer hemisphere below about z = 230 km and a thermally indirect cell above the direct cell near the solstice. The interhemispheric circulation transports haze particles from the summer to the winter hemisphere, causing a maximum haze opacity contrast near the solstice and a smaller contrast near the equinox, contrary to observation. On the other, if the GCM is run under modified cooling rate in order to account for the enhancement in nitrites and some hydrocarbons in the northern hemisphere near the vernal equinox, the meridional cell at the equinox becomes a single cell with rising motions in the autumn hemisphere. A more realistic haze opacity distribution can be reproduced at the equinox. However, a pure transport effect (without particle growth by microphysics, etc.) would not be able to cause the observed discontinuity of the global haze opacity distribution at any location. The stratospheric temperature asymmetry can be explained by a combination of asymmetric radiative heating rates and adiabatic heating due to vertical motion within the thermally indirect cell. A seasonal variation of haze particle number density is unlikely to be responsible for this asymmetry. It is likely that a thermally indirect cell covers the upper portion of the main haze layer. An artificial damping of the meridional circulation enables the formation of high-latitude jets in the upper stratosphere and weaker equatorial superrotation. The latitudinal temperature distribution in the stratosphere is better reproduced.

Atmosphere↗
PubMed2002

The influence of cigarette smoking on circulating concentrations of antioxidant micronutrients.

Cigarette smoke is a significant source of oxidative stress, one potential mechanism for its untoward health effects. The antioxidant defense system is partly comprised of antioxidant micronutrients, making it important to understand the relationship between cigarette smoking and circulating concentrations of antioxidant micronutrients. A synthesis of the literature shows that compared with nonsmokers, on average, active smokers have greater than 25% lower circulating concentrations of ascorbic acid, alpha-carotene, beta-carotene, and cryptoxanthin. The differences in blood concentrations of these micronutrients in former smokers is intermediate between never and current smokers, but average circulating concentrations of alpha-carotene, beta-carotene, and cryptoxanthin were 16-22% lower in former smokers compared with never smokers. Differences in dietary habits between smokers and nonsmokers could potentially account for these associations. Dietary micronutrient intake is associated with blood micronutrient concentrations. Furthermore, patterns of micronutrient consumption by smoking status mimic the pattern of associations observed for blood concentrations. For example, when pooled across studies intake of vitamin C was 16% lower in current smokers and 2% lower in former smokers than in never smokers; the corresponding figures for beta-carotene were 17 and 4%, respectively. Despite the strong potential for confounding, the differences observed between current smokers and nonsmokers seem to be due to an acute effect of smoking based on results of studies of smoking and antioxidant micronutrient concentrations that have either adjusted for dietary antioxidant micronutrient intake and other potential confounding factors or documented short term changes in circulating antioxidant micronutrient concentrations in smokers before and after smoking cigarettes. The associations observed with active smoking also appear to hold true for passive smoking, implying that even low-dose exposures to tobacco smoke can result in lowered circulating antioxidant micronutrient concentrations. Smoking was more weakly associated with circulating concentrations of vitamin E and the nonprovitamin A carotenoids lutein/zeaxanthin and lycopene. The combined evidence supports the conclusion that cigarette smoking is independently associated with lowered circulating concentrations of ascorbic acid and provitamin A carotenoids. These associations have implications for the design and interpretation of epidemiologic studies of antioxidant micronutrients in relation to health and disease. To the extent that these micronutrients are associated with health and longevity, this evidence documents yet another deleterious consequence of cigarette smoking on human health.

Antioxidants↗
PubMed2001

Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction.

OBJECTIVES: We investigated whether elevated levels of circulating monocyte-platelet aggregates (MPA) can be used to identify patients with acute myocardial infarction (AMI). BACKGROUND: Commonly used blood markers of AMI reflect myocardial cell death, but do not reflect the earlier pathophysiologic processes of plaque rupture, platelet activation and resultant thrombus formation. Circulating MPA form after platelet activation. METHODS: In a single center between October 1998 and November 1999, we measured circulating MPA in a blinded fashion by whole blood flow cytometry in 211 consecutive patients who presented to the emergency department (ED) with chest pain and were admitted to rule out AMI. Acute myocardial infarction was diagnosed by a CK-MB fraction greater than three times control. RESULTS: Patients with AMI (n = 61), as compared with those without AMI (n = 150), had significantly higher numbers of circulating MPA (11.6 +/- 11.4 vs. 6.4 +/- 3.6, mean +/- SD, p < 0.0001). After controlling for age, the adjusted odds of developing AMI for patients in the 2nd, 3rd and 4th quartiles of MPA, in comparison with patients in the lowest quartile (odds ratio = 1.0), were 2.1 (95% confidence interval [CI]: 0.7, 6.8), 4.4 (95% CI: 1.5, 13.1) and 10.8 (95% CI: 3.6, 32.0), respectively. The number of circulating MPA in patients with AMI presenting within 4 h of symptom onset (14.4) was significantly greater than those presenting after 4 h (9.4) and after 8 h (7.0), (p < 0.001). Of the 61 patients with AMI, 35 (57%) had a normal creatine kinase isoenzyme ratio at the time of presentation to the ED, but had high levels of circulating MPA (13.3). CONCLUSIONS: Circulating MPA are an early marker of AMI.

Creatine Kinase↗
PubMed1999

Circulating immune complexes and complement C4 null alleles in patients in patients operated on for premature atherosclerotic peripheral vascular disease.

Circulating immune complexes can lead to vascular inflammation and premature atherosclerosis and the fourth component of complement, C4, plays an important role in the removal of immune complexes. The objective of this study was to analyze the relation between circulating immune complexes and C4 null alleles in patients operated on for peripheral vascular disease before the age of 50. The prevalence of circulating immune complexes and null alleles of C4 (C4Q0) was determined in 62 patients with peripheral atherosclerosis requiring surgery before 50 years of age and in a matched control group. C4A and C4B null alleles (C4A*Q0, C4B*Q0) were determined by electrophoresis of plasma, followed by immunofixation. C4A and C4B concentrations were measured by ELISA. Circulating immune complexes were determined by sucrose density gradient centrifugation and gel filtration. There was no difference in the distribution of C4Q0 between patients and controls. The patients had higher prevalences and levels of circulating immune complexes. This was correlated with the presence of C4Q0, especially C4A*Q0. There was an inverse correlation of concentration of circulating immune complexes with C4A levels and with ratio of C4A/B levels. Thus, a significant proportion of patients with premature peripheral atherosclerosis had circulating immune complexes and C4A*Q0 enhanced the propensity to immune complex formation. This might represent one mechanism for vascular damage in this patient group.

Adult↗
PubMed2006

Weakening of tropical Pacific atmospheric circulation due to anthropogenic forcing.

Since the mid-nineteenth century the Earth's surface has warmed, and models indicate that human activities have caused part of the warming by altering the radiative balance of the atmosphere. Simple theories suggest that global warming will reduce the strength of the mean tropical atmospheric circulation. An important aspect of this tropical circulation is a large-scale zonal (east-west) overturning of air across the equatorial Pacific Ocean--driven by convection to the west and subsidence to the east--known as the Walker circulation. Here we explore changes in tropical Pacific circulation since the mid-nineteenth century using observations and a suite of global climate model experiments. Observed Indo-Pacific sea level pressure reveals a weakening of the Walker circulation. The size of this trend is consistent with theoretical predictions, is accurately reproduced by climate model simulations and, within the climate models, is largely due to anthropogenic forcing. The climate model indicates that the weakened surface winds have altered the thermal structure and circulation of the tropical Pacific Ocean. These results support model projections of further weakening of tropical atmospheric circulation during the twenty-first century.

Air Movements↗
PubMed2003

Design of passive mixers utilizing microfluidic self-circulation in the mixing chamber.

This paper proposes the design of a passive micromixer that utilizes the self-circulation of the fluid in the mixing chamber for applications in the Micro Total Analysis Systems (microTAS). The micromixer with a total volume of about 20 microL and consisting of an inlet port, a circular mixing chamber and an outlet port was designed. The device was actuated by a pneumatic pump to induce self-circulation of the fluid. The self-circulation phenomenon in the micromixer was predicted by the computational simulation of the microfluidic dynamics. Flow visualization with fluorescence tracer was used to verify the numerical simulations and indicated that the simulated and the experimental results were in good agreement. Besides, an index for quantifying the mixing performance was employed to compare different situations and to demonstrate the advantages of the self-circulation mixer. The mixing efficiencies in the mixer under different Reynolds numbers (Re) were evaluated numerically. The numerical results revealed that the mixing efficiency of the mixer with self-circulation was 1.7 to 2 times higher than that of the straight channel without a mixing chamber at Re= 150. When Re was as low as 50, the mixing efficiency of the mixer with self-circulation in the mixing chamber was improved approximately 30% higher than that in the straight channel. The results indicated that the self-circulation in the mixer could enhance the mixing even at low Re. The features of simple mixing method and fabrication process make this micromixer ideally suitable for microTAS applications.

Journal Article↗
PubMed1997

A single dose of intravenously injected poloxamine-coated long-circulating particles triggers macrophage clearance of subsequent doses in rats.

1. Adsorption of the block copolymer non-ionic surfactant poloxamine-908 on to the surface of polystyrene nanospheres (60 nm in diameter) produced 'phagocyte-resistant' particles (otherwise known as long-circulating particles). This was reflected by a profound reduction in uptake of such engineered nanospheres by macrophages of the reticuloendothelial system and extended blood circulation time, after intravenous administration to rats. 2. A single intravenous administration of poloxamine-908-coated particles dramatically affected the circulation half-life and body distribution of a second subsequent dose. The degree of alteration depended on the interval between the two doses. At 3 days after a single intravenous injection of poloxamine-coated particles, Kupffer cells and spleen macrophages could clear a second dose of long-circulating beads from the blood. When tested at day 14, the second dose of intravenously injected poloxamine-coated particles avoided rapid uptake by liver and spleen macrophages and remained in the blood. 3. The coating polymer (poloxamine-908) apparently triggered bead clearance by resident Kupffer cells and certain sub-populations of spleen macrophages, since a single intravenous dose of an endotoxin-free solution of poloxamine 3 days before the administration of long-circulating particles induced similar effects. When the interval between the two injections was 2 weeks, poloxamine-coated particles again exhibited long circulation half-life. This cycle could be repeated after intravenous administration of a second poloxamine dose 2 weeks after the first poloxamine injection. 4. The mechanism of particle recognition by resident tissue macrophages was found to be independent of opsonization processes. 5. These studies could have important implications in biomedical application, design and engineering of poloxamine-based long-circulating drug carriers for repeated intravenous administration.

Animals↗
PubMed1998

Molecular effects of sulphonylurea agents in circulating lymphocytes of patients with non-insulin-dependent diabetes mellitus.

AIMS: In circulating lymphocytes of NIDDM patients pyruvate dehydrogenase (PDH), the major determinant in glucose consumption through oxidative pathways, is poorly active. The aim of this study is to examine whether sulphonylurea drug treatment revives PDH activity in circulating lymphocytes from NIDDM patients. METHODS: Twenty normal-weight individuals with NIDDM were enrolled in this study. They had maintained their glycaemic levels close to normal by means of a restricted diet that had no longer been successful in the proceeding 2 months. The treatment protocol consisted in 160 mg gliclazide daily for 5 weeks. Twenty healthy subjects, matched for age, body mass index and gender, were enrolled as a control group. Patients, before and after treatment, as well as controls were tested for PDH activity in their circulating lymphocytes. Nine other untreated patients and nine healthy subjects, with the above mentioned characteristics, were recruited for the assay of PDH activity in their circulating lymphocytes before and after exposure, in vitro, to gliclazide, to insulin, and to gliclazide and insulin in combination. RESULTS: In gliclazide-treated NIDDM patients, PDH activity in circulating lymphocytes recovered. In vitro, in circulating lymphocytes of untreated patients and controls insulin at 5 microU ml(-1) was ineffective and highly effective, respectively, in raising enzyme activity; gliclazide at 10 ng ml(-1) was ineffective on PDH in both groups, but in combination with insulin at 5 microU ml(-1) in both groups PDH was as active as in cells of controls exposed to insulin only. In cells of controls, gliclazide alone at 25-50 ng ml(-1) caused enzyme activation, whereas above 50 ng ml(-1) it caused inhibition; in cells of patients below 50 ng ml(-1) it had no effects, but at 50 ng ml(-1) and above raised enzyme activity to the basal level of controls. CONCLUSIONS: This study suggests that free gliclazide concentrations determine recovery of PDH activity in circulating lymphocytes of treated patients through drug-mediated enhanced insulin control over PDH or through the drug alone.

Adult↗
PubMed1997

Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy.

OBJECTIVE: To investigate whether leptin is linked to reproduction, circulating levels were measured longitudinally throughout spontaneous menstrual cycles and during pregnancy in normal women. DESIGN: Longitudinal blood samples were collected from normal volunteers, either during regular menstrual cycles or during successful singleton pregnancies. PATIENTS: Six healthy, regularly cycling, women volunteers (31.5 +/- 3.0 years old, BMI = 21.6 +/- 0.5) were recruited for serial venous blood sampling throughout one complete menstrual cycle. In addition, five healthy, women (31.8 +/- 1.2 years old, pregnant BMI = 30.0 +/- 3.1) provided serial venous blood samples throughout one complete singleton pregnancy. MEASUREMENTS: Circulating venous oestradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), leptin and (pregnant group only) human chorionic gonadotrophin (hCG). RESULTS: In spontaneously cycling women, changes in circulating leptin levels were associated with menstrual phase (P < 0.001) and correlated with progesterone levels (P < 0.05). Peak leptin concentrations were recorded during the luteal phase (P < 0.01), coincident with maximal progesterone levels (P < 0.05). Leptin concentrations were elevated throughout gestation (P < 0.05), and especially during the second trimester (P < 0.05). Post-partum, circulating leptin levels fell sharply to below pregnant values. Leptin correlated with oestradiol (P < 0.05) and human chorionic gonadotrophin (hCG, P < 0.01) levels during pregnancy. First trimester (P < 0.05) and postpartum (P < 0.05) oestradiol concentrations and post-partum hCG levels exhibited the greatest correlation with circulating leptin. CONCLUSIONS: We conclude that the relationship between body mass index and circulating leptin varies during the course of spontaneous cycles in women, the best correlation occurring during the luteal phase when progesterone and leptin concentrations are highest. This, together with the correlation between circulating oestradiol, hCG and leptin levels during pregnancy, strongly suggests a dynamic relationship between leptin and reproductive events in women.

Adult↗
PubMed2003

Circulating RBC volume, measured with biotinylated RBCs, is superior to the Hct to document the hematologic effects of delayed versus immediate umbilical cord clamping in preterm neonates.

BACKGROUND: One problem assessing the hematologic physiology of preterm infants after delivery and/or the efficacy and toxicity of therapeutic interventions affecting RBC measurements is the inability of blood Hct values to accurately reflect circulating RBC volume-owing to changes in plasma volume that influence Hct (i.e., a fall in plasma volume concentrates RBCs to increase Hct; a rise in plasma volume dilutes RBCs to decrease Hct). STUDY DESIGN AND METHODS: As part of a randomized, clinical trial testing the hypothesis that delayed clamping of the umbilical cord at delivery expands neonatal circulating RBC volume, blood Hct was compared to circulating RBC volume results measured directly with autologous, biotinylated RBCs or estimated mathematically with neonatal body weight and Hct values in neonates after immediate or delayed (60 sec) cord clamping. RESULTS: Circulating RBC volume measured directly with biotinylated RBCs significantly increased (p=0.04) in neonates after delayed (42.1 +/- 7.8 mL/kg) versus immediate (36.8 +/- 6.3 mL/kg) cord clamping-a difference not detected indirectly by measuring Hct or estimating circulating RBC volume mathematically. CONCLUSIONS: Because true hematologic effects of delayed versus immediate cord clamping may not be apparent or may be misinterpreted, when based on indirect measurements of Hct or calculations of circulating RBC volume, it is important to measure circulating RBC volume directly-as done with autologous, biotinylated RBCs-to document whether delayed cord clamping truly results in a transfer of significant quantities of RBCs from placenta to neonate. The clinical benefits and potential toxicities of increased RBC transfer to neonates require further studies.

Biotin↗
PubMed2000

Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans.

To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm blood flow and arterial and venous levels of plasma nitrite, LMW-SNOs and HMW-SNOs, and red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest and during regional inhibition of NO synthesis, followed by forearm exercise. Surprisingly, we found significant circulating arterial-venous plasma nitrite gradients, providing a novel delivery source for intravascular NO. Further supporting the notion that circulating nitrite is bioactive, the consumption of nitrite increased significantly with exercise during the inhibition of regional endothelial synthesis of NO. The role of circulating S-nitrosothiols and SNO-Hb in the regulation of basal vascular tone is less certain. We found that low-molecular-weight S-nitrosothiols were undetectable and S-nitroso-albumin levels were two logs lower than previously reported. In fact, S-nitroso-albumin primarily formed in the venous circulation, even during NO synthase inhibition. Whereas SNO-Hb was measurable in the human circulation (brachial artery levels of 170 nM in whole blood), arterial-venous gradients were not significant, and delivery of NO from SNO-Hb was minimal. In conclusion, we present data that suggest (i) circulating nitrite is bioactive and provides a delivery gradient of intravascular NO, (ii) S-nitroso-albumin does not deliver NO from the lungs to the tissue but forms in the peripheral circulation, and (iii) SNO-Hb and S-nitrosothiols play a minimal role in the regulation of basal vascular tone, even during exercise stress.

Adult↗
PubMed2002

Increased expression of inducible nitric oxide synthase in circulating monocytes from patients with active inflammatory bowel disease.

BACKGROUND: Inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) synthesis are increased in epithelial cells and in tissue macrophages of the inflamed mucosa from patients with inflammatory bowel disease (IBD). Since tissue macrophages are derived from circulating monocytes, we studied iNOS expression in circulating monocytes and related this expression to disease activity. In view of the possible role of NO in monocyte function, we also studied iNOS expression in relation to markers of monocyte activation. METHODS: The expression of iNOS in circulating monocytes from 15 patients with active IBD, 6 patients who went into remission and 18 healthy controls was quantified by flow cytometry and correlated with surface markers (CD63, CD11b, HLA-DR) for monocyte activation. In addition, iNOS expression in circulating monocytes was assessed by Western blotting, immunocytochemistry and measurement of the NO metabolites nitrite and nitrate in plasma. RESULTS: The expression of iNOS in circulating monocytes and the percentage of iNOS-positive monocytes were increased in patients with active IBD compared to healthy controls (fluorescence index: 1.3 (0.1-6.3) versus 0.8 (0.0-1.8); P < 0.05: percentage of iNOS positive monocytes: 37.3 (1.0-77.0)% versus 5.3 (0.0-43.3)%; P<0.01). The six patients who went into remission all had a marked reduction of iNOS expression. iNOS expression was confirmed by Western blotting and immunocytochemistry. Plasma nitrite and nitrate levels were elevated in three patients with active 1BD. The surface markers for monocyte activation, CD63 and CD11b, were not elevated. HLA-DR expression was decreased on circulating monocytes from patients with active ulcerative colitis. CONCLUSIONS: iNOS is increased in circulating monocytes from patients with active IBD and this increased expression correlates with disease activity. Considering the decreased HLA-DR expression and absence of monocyte activation markers, NO produced by iNOS may have a function in suppressing systemic monocyte activation.

Adult↗
PubMed2006

Interleukin-8 is associated with circulating CD133+ progenitor cells in acute myocardial infarction.

AIMS: Release of progenitor cells is observed during inflammatory conditions and contributes to neovascularization. We, therefore, sought to investigate the relationship of circulating progenitor cells and interleukin (IL)-8 in acute myocardial infarction (AMI). METHODS AND RESULTS: From patients with stable angina and AMI, serial venous blood samples were obtained. The number of circulating CD133+CD45- progenitor cells, endothelial progenitor cells (EPCs), and circulating endothelial P1H12+CD45- cells was analyzed by flow cytometry. After stenting in patients with AMI, an increase in plasma IL-8 and vascular endothelial growth factor (VEGF) concentrations was observed, which was only minimal in patients with stable angina. Only in patients with AMI, this was followed by an increase in circulating CD133+CD45- progenitor cells. In contrast, circulating endothelial P1H12+CD45- cells and E-selectin RNA expression in peripheral blood were only elevated early in AMI, indicating shedding of activated endothelial cells. Multivariable analysis revealed an association of IL-8 and circulating CD133+CD45- progenitor cells in AMI, in addition to statin therapy and risk factor profile. CONCLUSION: In AMI, IL-8 is associated with circulating progenitor cells. In addition to the pro-angiogenic functions of IL-8 and VEGF, this mechanism may contribute to new vessel generation and, thereby, improve myocardial function.

AC133 Antigen↗