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PubMed1987

Molecular nature of three liver alkaline phosphatases detected by drug administration in vivo: differences between soluble and membranous enzymes.

1. Activities of alkaline phosphatase, liver-membranous, liver-soluble and serum-soluble, were dramatically induced in dogs by treatment with both phenobarbital and brovanexine. The treatment induced a 17-fold increase in membranous, a 155-fold increase in soluble, and a 105-fold increase in serum alkaline phosphatases. 2. There was no difference in the enzymatic behavior of the three forms of alkaline phosphatase, on heat stability, amino acid inhibition and optimum pH. 3. When the three alkaline phosphatases were treated initially with n-butanol, their apparent molecular size was identical. After treatment with phosphatidylinositol-specific phospholipase C, the liver-soluble and serum-soluble alkaline phosphatase were of the same molecular size. Liver-membranous alkaline phosphatase, however, was larger in molecular size than the other two forms, suggesting a difference between soluble and membranous alkaline phosphatase forms. 4. In terms of the sugar moiety of the three alkaline phosphatase forms, the membranous enzyme showed more of the higher affinity fraction and less of the lower affinity fraction of concanavalin A, compared with the soluble enzymes. 5. Consequently, it is possible that the membranous enzyme may be solubilized by an enzyme such as phosphatidylinositol-specific phospholipase C and modify further the sugar moiety of alkaline phosphatase molecules, resulting in serum alkaline phosphatase transfer from the soluble enzyme in liver.

Alkaline Phosphatase↗

PubMed1996

Growth cone behavior in the presence of soluble chondroitin sulfate proteoglycan (CSPG), compared to behavior on CSPG bound to laminin or fibronectin.

Proteoglycans (PGs) are complex macromolecules of the extracellular matrix (ECM) that have a wide variety of effects on developing and regenerating neurons in vivo and in vitro. One hypothesis regarding the mechanisms of PG regulation of neuronal behavior states that the conformation of PGs may be critical, and thus that ECM- or cell surface-bound PGs may operate differently than secreted (soluble) PGs. Therefore, this study examined differences between the effects of soluble chondroitin sulfate proteoglycan (CSPG) and substratum-bound CSPG on neuronal growth cone behavior. Dissociated chicken dorsal root ganglion (DRG) neurons were cultured on either laminin (LN) or fibronectin (FN), both sensory neurite outgrowth-promotin glycoproteins. CSPG (or chondroitin sulfate alone) was either bound to FN or LN, or was added to the culture media. Subsequently, using time lapse video microscopy and image analysis, this study measured: (1) neuronal attachment, (2) neurite outgrowth, (3) rate of neurite elongation, and (4) filopodial length and lifespan. To determine the site of CSPG action, DRG neurons were grown on either: CS-1, a FN peptide [Humphries M. J. et al. (1987) J. biol. Chem. 262, 6886-6892], or a recombinant FN protein, RFNIIIcs (Maejne, submitted), both of which permit DRG attachment and outgrowth but do not have recognized CSPG binding sites, and the resulting neuronal behavior was compared to that of DRG neurons grown on intact FN. The results of these studies confirm that the effect of CSPG on DRG neurons is concentration-, conformation- and substratum-dependent. On I.N, soluble CSPG had little to no effect on neurite initiation or outgrowth, while substratum-bound CSPG inhibited neurite outgrowth. In contrast, on FN, soluble CSPG inhibited neurite outgrowth and decreased the rate of neurite elongation. Soluble CSPG did not affect the length of sensory growth cone filopodia or filopodial lifespan on either LN or FN. From the FN fragment experiments, we found that: (1) soluble CSPG reduces neurite outgrowth on FN or FN fragments, but not on LN, up to 80%, and reduces elongation rate on FN up to 50%, and (2) soluble CSPG regulates neuronal behavior by binding directly to growth cones elongating on FN. Given that substratum-bound CSPG from a variety of sources is inhibitory to neurite outgrowth and to the rate of neurite elongation, while soluble CSPG often has different effects on growth cone behavior, the regulation of growth cone behavior by CSPGs may be dependent upon CSPG conformation. Further, CSPG may affect growth cone behavior by either binding to the substratum or by binding directly to growth cones.

Animals↗

PubMed1994

Serum soluble IL-2 receptor (sIL-2R) and eosinophil cationic protein (ECP) levels in atopic dermatitis.

We examined the serum soluble IL-2 receptor and eosinophil cationic protein levels in patients with atopic dermatitis (n = 21), patients with urticaria (n = 12), and normal healthy individuals (n = 14). We found that both soluble IL-2 receptor levels and eosinophil cationic protein levels were significantly higher in atopic dermatitis than in urticaria or normal controls. Although both soluble IL-2 receptor levels and eosinophil cationic protein levels were significantly correlated with clinical severity scores in atopic dermatitis, the correlation between eosinophil cationic protein levels and clinical severity scores was higher than that between soluble IL-2 receptor levels and clinical severity scores. However, soluble IL-2 receptor levels, eosinophil cationic protein levels and clinical severity scores were not significantly correlated with IgE levels. The chronological changes of soluble IL-2 receptor and eosinophil cationic protein levels differ from patient to patient. However, levels of soluble IL-2 receptor and eosinophil cationic protein seem to parallel to each other in 65% of patients with AD. Measurement of serum eosinophil cationic protein or soluble IL-2 receptor levels may be a useful tool to monitor the short-term or long-term disease activity of atopic dermatitis in conjunction with clinical severity scores.

Adolescent↗

PubMed2005

Maternal serum soluble fms-like tyrosine kinase 1 concentrations are not increased in early pregnancy and decrease more slowly postpartum in women who develop preeclampsia.

OBJECTIVE: We measured maternal serum soluble fms-like tyrosine kinase 1 concentrations across pregnancy and immediately postpartum in women who developed preeclampsia and normal pregnant women. STUDY DESIGN: This was a nested case control study of 113 normal pregnant women and 55 women with preeclampsia. RESULTS: Serum soluble fms-like tyrosine kinase 1 concentrations increased similarly in early pregnancy in both groups. Mean serum soluble fms-like tyrosine kinase 1 concentrations were increased in women who developed preeclampsia, compared with normal pregnant women, and this increase was most pronounced in severe preeclampsia. However, many women with preeclampsia had soluble fms-like tyrosine kinase 1 concentrations similar to normal pregnant women. Lastly, soluble fms-like tyrosine kinase 1 decreased rapidly after delivery, but this decrease was significantly slower in women with severe preeclampsia. CONCLUSION: Increased soluble fms-like tyrosine kinase 1 is not an early-pregnancy event among women who later develop preeclampsia. Increased soluble fms-like tyrosine kinase 1 is more likely to be present in women with severe preeclampsia, but it is not present in all women with preeclampsia. Soluble fms-like tyrosine kinase 1 concentrations decrease more slowly after delivery in women with preeclampsia, consistent with a decreased rate of excretion or continued production.

Adult↗

PubMed2005

Soluble alpha2-macroglobulin receptor is increased in endotracheal aspirates from infants and children after cardiopulmonary bypass.

OBJECTIVE: Cytokine dysregulation contributes to the systemic inflammatory response after cardiopulmonary bypass. Clearance of cytokine binding proteins may be important in the resolution of inflammation. Our aim was to determine whether the cytokine binding protein alpha 2 -macroglobulin and its soluble receptor were upregulated in endotracheal aspirates from infants and children undergoing cardiopulmonary bypass. METHODS: Seventy tracheal aspirates were collected before and after cardiopulmonary bypass from 35 infants and children undergoing surgical correction of congenital heart defects. alpha 2 -Macroglobulin and the soluble alpha 2 -macroglobulin receptor were identified by Western blot. With the use of multi-analyte cytokine profiling, pro-inflammatory and anti-inflammatory cytokines were quantified, normalized to total protein, and expressed as ratios. Paired t tests and Wilcoxon signed-rank tests were performed between prebypass and postbypass samples. Correlations were examined among alpha 2 -macroglobulin, soluble alpha 2 -macroglobulin receptor, cytokine ratios, and the clinical variables of cardiopulmonary bypass, aortic crossclamp, and circulatory arrest times. RESULTS: alpha 2 -Macroglobulin increased by 50% (mean densitometry increase 82,683 +/- 184,594, P = .012), and soluble alpha 2 -macroglobulin receptor increased by 17% (mean densitometry increase 506,148 +/- 687,037, P = .0001) after cardiopulmonary bypass. The ratio of interleukin-8/interleukin-4 increased by 136% ( P = .0001), and interleukin-8/interleukin-10 increased by 102% ( P = .001). The increase in soluble alpha 2 -macroglobulin receptor was positively correlated with the ratios of interleukin-8/interleukin-4 and interleukin-8/interleukin-10. There were no statistically significant positive correlations between the increase in alpha 2 -macroglobulin or soluble alpha 2 -macroglobulin receptor and measured clinical variables. CONCLUSIONS: We report for the first time the upregulation of alpha 2 -macroglobulin and soluble alpha 2 -macroglobulin receptor in tracheal aspirates after cardiopulmonary bypass in infants and children. Soluble alpha 2 -macroglobulin receptor correlates with increased alpha 2 -macroglobulin and a disproportionate increase in pro-inflammatory to anti-inflammatory cytokine ratios.

Age Factors↗

PubMed1998

Serial changes in plasma levels of soluble P-selectin in patients with acute myocardial infarction.

The present study examines whether an acute inflammatory response occurs during acute myocardial infarction (AMI) by measuring soluble P-selectin levels. We examined plasma soluble P-selectin levels in 16 consecutive patients with AMI, in 15 patients with angina, and in 13 control subjects with chest pain but normal coronary arteries and no coronary spasm. In patients with AMI, blood samples were obtained immediately after admission and at 1, 4, 24, and 48 hours, and 1 week after initiation of reperfusion therapy. The plasma soluble P-selectin levels were significantly higher in the AMI group on admission than in the other 2 groups (83 +/- 13 ng/ml, p < 0.01). The plasma soluble P-selectin levels at baseline were not significantly different between the angina and control groups (28 +/- 4 vs 24 +/- 5 ng/ml, p = NS). Plasma soluble P-selectin levels reached their peak significantly at 4 hours after initiation of the reperfusion therapy in patients with AMI. The peak level was significantly higher than the level on admission (115 +/- 17 vs 83 +/- 13 ng/ml, p < 0.05). The plasma soluble P-selectin levels were higher in the AMI group than in the angina and control groups over the time course (p < 0.01). Our data indicate that the plasma soluble P-selectin levels are increased in patients with AMI, and that the levels are increases after reperfusion therapy more than before reperfusion. We suggest that the increase in the plasma soluble P-selectin levels may be caused by the activation of endothelial cells and platelets after myocardial ischemia and reperfusion during AMI.

Aged↗

PubMed2000

Effects of nasal continuous positive airway pressure on soluble cell adhesion molecules in patients with obstructive sleep apnea syndrome.

PURPOSE: Obstructive sleep apnea syndrome is common in middle-aged men and may be associated with an increased risk of cardiovascular disease. We investigated the effect of nasal continuous positive airway pressure (CPAP) treatment on levels of soluble cell adhesion molecules-which have been shown to be associated with the development of atherosclerosis-in these patients. SUBJECTS AND METHODS: We studied 23 patients with obstructive sleep apnea syndrome diagnosed by polysomnography who were treated with nasal CPAP. Serum soluble intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 levels were measured before nasal CPAP was started, and after 3 or 4 days (n = 19), 1 month (n = 23), or 6 months (n = 11) of treatment. RESULTS: After 3 to 4 days of nasal CPAP therapy, the mean (+/- SD) soluble E-selectin level had decreased from 89 +/- 44 ng/mL to 69 +/- 28 ng/mL (P = 0.002). After 1 month, the soluble intercellular adhesion molecule-1 level had decreased from 311 +/- 116 ng/mL to 249 +/- 74 ng/mL (P = 0.02). After 6 months, soluble vascular cell adhesion molecule-1 levels had not changed significantly, while the mean soluble intercellular adhesion molecule-1 level (212 +/- 59 ng/mL) had decreased further (P = 0.02). Before treatment, soluble intercellular adhesion molecule-1 levels and the apnea and hypopnea index were correlated (r = 0.43, P = 0.04). CONCLUSIONS: Obstructive sleep apnea and hypopnea have a significant adverse effect on serum soluble cell adhesion molecule-1 levels that may be reduced by nasal CPAP treatment.

Adult↗

PubMed1998

Soluble interleukin-2 receptor in children with reflux nephropathy.

PURPOSE: Serum soluble interleukin-2 receptor level is a sensitive and quantitative marker of lymphocyte activation. We determined levels of serum soluble interleukin-2 receptor in children with reflux nephropathy to evaluate its clinical significance in the prediction for the progression of renal injuries. MATERIALS AND METHODS: Serum soluble interleukin-2 receptor values were determined in 63 children with reflux nephropathy. The group consisted of 37 boys and 26 girls 10 to 18 years old. T cells (naive and memory), B cells and macrophages were evaluated immunohistochemically in the scarred kidneys of 4 other patients (3 boys and 1 girl 5 to 16 years old) who underwent nephrectomy due to severe reflux nephropathy with little function seen on (99m)technetium-dimercapto-succinic acid (DMSA) renal scan. Levels of serum soluble interleukin-2 receptor were measured by an enzyme-linked immunosorbent assay. We simultaneously determined serum levels of creatinine and beta2-microglobulin, and urinary levels of alpha1-microglobulin and microalbumin. Individual functions of the right and left kidneys were estimated by renal dimercaptosuccinic acid uptake. RESULTS: Levels of serum soluble interleukin-2 receptor in the patients who had low total uptake of DMSA (right uptake plus left uptake) were significantly higher than those from patients with normal total uptake. Levels of serum soluble interleukin-2 receptor correlated significantly with levels of creatinine (r=0.616, p <0.0001) and beta2-microglobulin (r=0.803, p <0.0001), and levels of urinary alpha1-microglobulin (r=0.753, p <0.0001) and microalbumin (r=0.673, p <0.0001). A significant negative correlation was observed between levels of serum soluble interleukin-2 receptor and total DMSA uptake values (right uptake plus left uptake r=-0.678, p <0.0001). In the scarred kidneys leukocyte infiltrates were markedly increased in fibrosed spaces. The predominant cell type in these lesions was memory T cells. CONCLUSIONS: These results suggest that elevated levels of serum soluble interleukin-2 receptor are likely to reflect activated T cells in the kidneys of patients with reflux nephropathy and may be a useful predictor of progression of renal injury in these children.

Adolescent↗

PubMed2000

Amniotic fluid--soluble vascular endothelial growth factor receptor-1 in preeclampsia.

OBJECTIVE: To measure the levels of the soluble receptor for the potent angiogenic agent vascular endothelial growth factor (VEGF) in amniotic fluid (AF) in healthy and complicated pregnancies, and compare them with levels of erythropoietin, another factor upregulated by hypoxia. METHODS: We assessed amniotic fluid from the second (n = 35, gestational weeks 14-19) and third (n = 29) trimesters of healthy women, and from the third trimesters of preeclamptic (n = 22) and diabetic women with (n = 11) or without preeclampsia (n = 34) and from women with fetal growth restriction (FGR) (n = 14) for soluble VEGF receptor-1 (VEGFR-1) by enzyme-linked immunosorbent assay. RESULTS: In early normal pregnancy, AF-soluble VEGFR-1 levels were higher (median 22 ng/mL, range 2.3-29.5 ng/mL) than in the third trimester (median 13 ng/mL, range 0.5-32 ng/mL; P < .05). In preeclamptic women during the third trimester, levels were higher (median 20 ng/mL, range 10.5-37 ng/mL; P < .05) than healthy controls. The lowest third-trimester levels were in diabetic women (median 11 ng/mL, range 0.5-27 ng/mL). In women with preeclampsia and diabetes, AF-soluble VEGFR-1 levels remained lower (median 13, range 6-32 ng/mL; P < .05) than in women with preeclampsia alone. Amniotic fluid levels of soluble VEGFR-1 in women with FGR (median 19.5 ng/mL, range 5-40 ng/mL) did not statistically differ from those of controls. The AF levels of soluble VEGFR-1 did not correlate with those of erythropoietin. Soluble VEGFR-1 was clearly detectable (median 14 ng/mL, range 9-22 ng/mL) in culture media from placental biopsies (n = 20). CONCLUSION: Preeclampsia is associated with increased levels of soluble VEGFR-1, which are independent of erythropoietin, another hypoxia-inducible factor.

Amniotic Fluid↗

PubMedDate not supplied

Delayed onset of action of soluble insulin after premixing with U100 lente insulin.

In previous studies we demonstrated that mixing lente with soluble insulin of U40 strength in the syringe delays the onset of action of soluble insulin. Lente insulin of U100 as compared to U40 strength, contains a proportionally smaller amount of excess of zinc. The purpose of our study was to investigate the effect of premixing lente and soluble insulin of U100 strength on plasma insulin levels and glucose requirements during glucose clamping for 8 h in eight healthy volunteers. Soluble (0.22 U/kg) and lente (0.33 U/kg) insulin were administered once separately and once immediately after mixing in the syringe. In both instances the insulins were injected into two depots in contralateral thighs. The initial rise of plasma insulin levels from 0 to 2 h was not significantly different for both studies: from 11 +/- 1 to 25 +/- 4 mU/l and from 10 +/- 1 to 31 +/- 5 mU/l after premixing and separate administrations, respectively. However, the areas under the curves of the glucose infusion rates were significantly greater from 0 to 2 h after the separate injections of soluble plus lente than after premixing 3.25 +/- 0.70 vs. 1.84 +/- 0.56 mmol/kg, respectively (P less than 0.05). Plasma insulin levels and glucose requirements were significantly higher after premixing, compared with separate injections of soluble plus lente, from 300 to 480 and from 405 to 480 min, respectively. We conclude that mixing soluble with lente insulin of U100 strength in the syringe delays the onset of action of soluble insulin.

Adult↗

PubMed1998

Serum levels of soluble Fas antigen in chronic hepatitis C patients.

BACKGROUND/AIMS: In chronic hepatitis C, the expression of Fas antigen on hepatocytes is upregulated and Fas ligand expression is detected on liver-infiltrating mononuclear cells. Thus Fas antigen/Fas ligand-mediated apoptosis is thought to be involved in hepatic injury in chronic hepatitis C. The soluble form of Fas antigen has been detected in serum and shown to inhibit Fas-mediated apoptosis. The present study was done to evaluate the relationship of serum soluble Fas antigen levels with disease activity. METHODS: Serum soluble Fas antigen levels were measured by enzyme-linked immunosorbent assay for 68 chronic hepatitis C patients and compared with those in normal volunteers, chronic hepatitis B patients and autoimmune hepatitis patients. These levels were compared with histological activity, ALT levels, HCV-RNA titer and Fas expression on hepatocytes. RESULTS: Serum soluble Fas antigen levels in chronic hepatitis C patients (3.24+/-1.55 ng/ml) were significantly higher than those in normal volunteers (1.70+/-1.01 ng/ml) (p<0.01). They showed no difference from those in chronic hepatitis B or autoimmune hepatitis patients. Histologically, soluble Fas antigen levels showed correlation with the levels of liver inflammation (p<0.01). However, no relationship was observed between serum soluble Fas antigen and serum ALT levels or HCV-RNA titer. Serum soluble Fas antigen levels showed correlation with the levels of Fas antigen expression in liver tissue (p<0.05). CONCLUSIONS: These findings suggest that serum soluble Fas antigen may reflect the expression levels of Fas antigen on hepatocytes and the severity of liver inflammation in chronic hepatitis C.

Adult↗

PubMed2000

Solubility of lead, zinc and copper added to mineral soils.

Elevated levels of heavy metals in soils are a result of industrial activities, atmospheric deposition, and the land application of sewage sludges and industrial by-products. Their persistence in the soil environment has created interest in the possible changes in solubility. In this study, total dissolved concentrations of Pb, Zn, and Cu were monitored in seven metal-amended soils (a calcareous and six acid mineral soils). Single metal solutions were added to soils and equilibrated (aged) for 40 days. During the 40 days the soil was allowed to air-dry and was rewetted in cycles of about 5 days. At the end of this reaction period, metal solubility was measured (by atomic absorption spectrometry and direct current plasma spectrometry) at the initial soil pH and at decreased pH values which were induced by addition of small aliquots of acid. As expected, solubility of added Pb, Zn, and Cu increased with a decrease in pH. Furthermore, the results showed that the solubility relationship with pH was similar in all non-calcareous soils. This suggests that metal solubility may be controlled by similar soil components, presumably involving soil characteristics such as pH, organic matter content, and soil mineralogy. For each metal, an approximate pH value was found at which solubility deviated from the solubility of metals when they occur in soils at typical (natural) values. This pH was about (pH+/-0.2): 5.2 for Pb, 6.2 for Zn, and 5.5 for Cu. Thus, pH values below these thresholds may enhance metal mobility, biological availability and toxicity in soils. Metals dissolved at higher pH in the calcareous soil (18.8 g kg(-1) inorganic carbon, initial pH 8.2). In a calcareous soil, a significant fraction of these metals react with carbonates, and decreased pH results in much higher metal dissolution. Yet, metal solubility in soils is not determined by the formation and dissolution of single metal compounds.

Journal Article↗

PubMed2000

Relation of enhanced Pb solubility to Fe partitioning in soils.

It is well documented that Pb solubility may be related to Fe chemistry in soils and enhanced Pb solubility may occur under certain reducing conditions; however, quantification of such relationships is unavailable. Based on metal classification, Pb (II) and Fe (II) are similar in some chemical characteristics. Thus, competition between Pb and Fe for ligands in soils may be important in determining Pb solubility. In this paper, Pb solubility was examined in a sandy soil after spiking with Pb and incubating for 40 days under water-flooded or non-water-flooded conditions. Solution chemistry in soil columns was adjusted using different concentrations of NaCl, CaCl(2) and deionized water of varying pH before incubation. The results showed that Pb solubility in the soil was not correlated well with pH, dissolved organic C or aqueous Fe concentrations. However, an index of Fe partition behavior using the ratio of aqueous Fe to sorbed Fe was related to Pb solubility. Enhanced Pb solubility occurred only when the index was < approximately 2 kg l(-1). The index can be a simple measure of Fe's ability to compete with Pb for ligands in solution. The ability of Fe to compete with Pb decreases as the index decreases and as the ratio approached its minimum, substantial increases in Pb solubility will be expected. In general, the index was not sensitive to changes in solution chemistry. A similar trend was observed using one data set published in the literature.

Journal Article↗

PubMedDate not supplied

Effects in humans of intravenously administered endotoxin on soluble cell-adhesion molecule and inflammatory markers: a model of human diseases.

1. Endotoxin, a component of the cell wall of Gram-negative bacteria, could be a predisposing mediator of many pathological disorders. The present study was undertaken to determine the effects and time-course of acute endotoxin challenge on inflammatory and cell-adhesion molecule markers shedding in the plasma as potential surrogates. 2. Six normal male subjects per group (age range 21-35 years) were injected with 4 ng/kg, i.v., reference standard Escherichia coli (0113:h10:k) endotoxin or physiological saline. 3. Plasma inflammatory markers (tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and TNF-receptor I (RI)) and cell-adhesion molecule markers (soluble L-selectin, soluble P-selectin, soluble vascular cell adhesion molecule (VCAM)-1) were determined using sensitive and specific ELISA. 4. Tumour necrosis factor-alpha increased from a basal level of 2.8 pg/mL to approximately 800 pg/mL at 90 min after endotoxin. Similarly, IL-6 peaked 2-3 h after endotoxin injection, with a rapid decline by 6-8 h, and levels returned to basal values by 24 h. 5. In contrast, TNF-RI peaked at 2 h (increasing from basal levels of 900-3300 pg/mL) with a much slower decline and without return to basal levels at 24 h (1400 pg/mL). 6. Endotoxin resulted in a rapid rise in soluble L-selectin within 1 h, which increased from a basal of 150-425 ng/mL. This rapid rise in soluble L-selectin was sustained for up to 2.5 h and then rapidly declined to basal levels by 3.5 h. 7. In contrast, plasma soluble P-selectin levels showed a delayed and progressive increase up to 8 h (increasing from a basal level of 50-95 ng/mL), with a partial decline at 24 h (80 ng/mL). 8. Similarly, soluble VCAM-1 levels showed a progressive rise up to 24 h (increasing from basal values of 600-1000 ng/mL). 9. This acute human model of endotoxin exposure demonstrated an upregulation of inflammatory stimuli leading to a short-term hyperactivation of leucocytes and a more sustained activation of platelets and endothelium. 10. This model provides a non-invasive method for studying the complex effects of endotoxin-like pathogens on different cellular events using soluble plasma surrogate markers.

Adult↗

PubMed2000

Plasma-soluble E-selectin after cardiopulmonary bypass in children: is it a marker of the postoperative course?

OBJECTIVE: To investigate the relationship and possible role of soluble adhesion molecule E-selectin in the postoperative course in children undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective cohort study. SETTING: Pediatric intensive care unit of a university hospital. PARTICIPANTS: Thirteen children who were candidates for cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serial blood samples of 13 CPB patients were collected from the arterial catheter or from the bypass circuits preoperatively; on initiation of CPB; on termination of CPB; and 1, 2, 4, 8, 12, 18, 24, and 48 hours postoperatively. Plasma was recovered immediately, aliquoted, and frozen at -70 degrees C until use. Circulating soluble selectin molecules were measured with a sandwich enzyme-linked immunosorbent assay technique. There were significant changes in plasma levels of soluble E-selectins in patients after CPB, and these levels were associated with patient characteristics, operative variables, and postoperative course. Soluble E-selectin correlated significantly with inotropic support and the use of anti-inflammatory drugs. There was a significant association between the development of postoperative sepsis and soluble E-selectin levels. No correlation was found between soluble E-selectins and duration of CPB, aortic cross-clamping, or hemodynamic variables, including heart rate and mean systemic arterial pressure. CONCLUSION: These results suggest a relationship between CPB-induced mediators and early and late clinical effects. Although the mechanism for the increase of soluble E-selectin remains to be elucidated, the upregulation of soluble E-selectin indicates neutrophil activation, and its inhibition may represent a target for reducing the inflammatory response associated with CPB.

Cardiopulmonary Bypass↗

PubMed1999

Inflammatory parameters and soluble cell adhesion molecules in Swedish children with Kawasaki disease: relationship to cardiac lesions and intravenous immunoglobulin treatment.

The possible use of inflammatory parameters as a predictor of coronary artery lesions (CAL) and the effect of intravenous immunoglobulin (IVIG) treatment in 30 Swedish children with acute Kawasaki disease were investigated. All the patients were treated with IVIG (2 g/kg) and seven of them had CAL. Ten febrile children, hospitalized for treatment of severe infection, and 15 healthy children served as controls. The levels of soluble E-selectin and soluble intercellular adhesion molecule (ICAM)-1 in the Kawasaki patients were elevated in comparison to healthy, but not in comparison to febrile controls. Paired analysis of our patients before and after IVIG therapy during acute disease revealed lowered levels of C-reactive protein, interleukin-6, soluble E-selectin and soluble ICAM-1. We found no statistically significant relationships among any of these parameters as a possible predictor of CAL, but three patients with cardiac sequelae demonstrated high values for these inflammatory parameters. These findings may reflect endothelial activation in connection with vasculitis, and the anti-inflammatory effect of IVIG treatment lowering cytokine levels and subsequently decreasing the expression and shedding of adhesion molecules. In conclusion, we were unable to identify a predictor of CAL in the acute phase. The patients had higher levels of soluble E-selectin and soluble ICAM-1 than did afebrile controls, but not febrile controls. The patients' levels of C-reactive protein, interleukin-6, soluble E-selectin and soluble ICAM-1 were decreased after 1-2d of IVIG treatment.

C-Reactive Protein↗

PubMed2004

Thyrocytes isolated from autoimmune-diseased thyroids secrete soluble tumor necrosis factor-R1 that is related to their elevated protein kinase C activity.

Soluble tumor necrosis factor (TNF)-alpha receptors have the potential to modulate TNF-alpha activity during autoimmune thyroiditis. In this study we examined cell-surface TNF-alpha receptors and soluble TNF-alpha receptor production by thyrocytes from normal and MRL-lpr(-/-) (diseased) mice, which spontaneously develop autoimmune thyroiditis. We found that murine thyrocytes possess the 55-kd receptor (TNF-R1). Examination of soluble TNF-R1 production revealed that diseased thyrocytes produced sevenfold more soluble TNF-R1 than normal thyrocytes. Furthermore, basal protein kinase C (pKC) activity in diseased thyrocytes was 67% higher than that found in normal murine thyrocytes. The elevated basal pKC activity in diseased thyrocytes was related to their enhanced production of soluble TNF-R1 because inhibition of pKC activity with calphostin C caused soluble TNF-R1 production to decrease significantly. Additionally, soluble TNF-R1 production by murine thyrocytes was not a result of cell-surface receptor shedding but through secretion of a truncated version of TNF-R1. This was evident when cell-surface TNF-R1 levels were unchanged after treatment of diseased thyrocytes with calphostin C. Also, the 28-kd form of TNF-R1, which corresponds to the soluble receptor, was present in the intracellular membranes of the diseased thyrocytes.

Animals↗

PubMed1994

Increased plasma concentrations of soluble tumor necrosis factor receptors in sepsis syndrome: correlation with plasma creatinine values.

OBJECTIVES: Tumor necrosis factor (TNF) is an important mediator in the complex pathophysiology of sepsis syndrome. Although a positive correlation with mortality rate has been demonstrated, TNF has not been found consistently in sepsis. Since prolonged increases in soluble TNF receptor concentrations were demonstrated after endotoxin and TNF administration, we investigated whether the measurement of TNF receptor concentrations could provide a better indicator of disease than plasma TNF and interleukin (IL)-6 concentrations. DESIGN: Prospective analysis. SETTING: General intensive care unit (ICU) of a university hospital. PATIENTS: Twenty-six patients with sepsis syndrome and proven bacteremia. MEASUREMENTS AND MAIN RESULTS: Plasma peak concentrations of the soluble 55-kilodalton molecular weight TNF receptor were significantly higher (p < .005) in nonsurvivors compared with survivors of sepsis syndrome, whereas the difference in peak concentrations of the soluble 75-kilodalton TNF receptor did not reach significance (p = .06). In contrast to TNF peak concentrations (p = .14), significantly higher (p < .05) IL-6 peak concentrations were measured in nonsurvivors. Besides the positive correlation between the soluble 55-kilodalton TNF receptor and the soluble 75-kilodalton TNF receptor (r2 = .68; p < .0001), peak concentrations of both soluble 55-kilodalton TNF receptor and 75-kilodalton TNF receptor correlated significantly with plasma creatinine values, an indicator of renal function (r2 = .60; p < .0001 and r2 = .44; p < .001, respectively). Plasma creatinine concentrations were significantly higher in nonsurvivors (p < .001). CONCLUSIONS: In the population studied, plasma-soluble TNF receptor concentrations correlated with outcome as well as with plasma creatinine concentrations. The data presented suggest that increased plasma-soluble TNF receptor concentrations in patients with sepsis syndrome are merely the result of renal failure complicating sepsis, and are similarly correlated with mortality rate.

Adult↗