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Soluble vascular cell-adhesion molecule-1 and soluble intercellular adhesion molecule-1 correlate with lipid and apolipoprotein risk factors for coronary artery disease in children.

UNLABELLED: Atherosclerosis begins in childhood and progresses from fatty streaks to raised lesions in adolescence and young adulthood. This process is accelerated in children with risk factors for coronary artery disease (CAD). Cell adhesion molecules (CAMs) are supposed to play important roles in the initial development of atherosclerosis, which may suggest that the expression of CAMs is increased in children more than in older subjects or in CAD patients. To determine whether risk factors for CAD are associated with an increased expression of CAMs, we investigated the relationships of the serum levels of soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1) and soluble P-selectin (P-selectin) with lipid and apolipoprotein parameters in children (40 boys and 45 girls). We also examined the relationships between soluble CAMs and the fractional esterification rate of cholesterol in HDL (FER(HDL)), particle size of LDL and lipoprotein containing apoA-I, but no apoA-II (LpA-I). In children, soluble VCAM-1 levels were correlated with the levels of triglyceride (in boys) and apoB, the ratio of apoB to apoA-I and FER(HDL) (in girls). Similar associations were found for soluble ICAM-1. Furthermore, the soluble ICAM-1 level was inversely correlated with LpA-I level, LDL size (in boys) and HDL cholesterol level (in girls). Soluble P-selectin levels were not correlated with these parameters. CONCLUSION: Our data indicate that intervention to normalize risk factors for coronary artery disease should be started at a young age to prevent increased expression of cell adhesion molecules.

Adolescent↗

Comparison of cellular schizont, soluble schizont and soluble piroplasm antigens in ELISA for detecting antibodies against Theileria annulata.

The efficacy and suitability of cellular schizont, soluble schizont and soluble piroplasm antigens was compared for detecting antibodies against Theileria annulata. Fifty bovine sera of known identity were evaluated in ELISA using the above mentioned antigens. Antibody titres of 1:100 to 1:51,200 were detected while using soluble piroplasm and cellular schizont antigen in ELISA. The titres ranged between 1:100 to 1:25,600 with the soluble schizont antigen. Soluble piroplasm antigen exhibited the highest antibody titres followed by cellular schizont and soluble schizont antigens. Cellular schizont antigen proved to be better than soluble schizont antigen for detecting anti-schizontal antibodies. Antibody titres obtained by the three antigens exhibited a good linear correlation amongst each other. The study showed that soluble piroplasm and cellular schizont antigens can be used successfully for detecting antibodies against piroplasm and schizont stages of T. annulata, respectively in bovine sera.

Animals↗

Soluble thrombomodulin activity and soluble thrombomodulin antigen in plasma.

Endothelial cell membrane-bound thrombomodulin (TM) plays a critical role as a cofactor in the protein C pathway, important in regulating coagulation as well as inflammation. Heterogeneous soluble TM fragments circulate in the plasma and are found at increased levels in various diseases such as cardiovascular disease and diabetes, and in ischemic and/or inflammatory endothelial injuries. The anticoagulant function of these soluble fragments has not been measured in healthy individuals or in patients. Using an immobilized monoclonal antibody against TM and a microtiter plate format, an assay was designed to capture the soluble TM fragments in plasma and measure their cofactor activity in the thrombin-mediated activation of protein C. In addition, soluble TM antigen levels were measured by enzyme-linked immunosorbent assay. Both assays were used to investigate a group of healthy blood donors. TM fragments released into plasma were shown to retain significant cofactor activity, and reference intervals for healthy men and women were established. Furthermore, a statistically significant correlation was observed between soluble TM antigen levels and soluble TM cofactor activity. This notwithstanding, soluble TM activity only accounted for a minor part of all variation in soluble TM antigen levels (R2 = 22% in men and R2 = 16% in women).

Adolescent↗

Extended Hildebrand solubility approach: solubility of theophylline in polar binary solvents.

A quantitative approach is presented for predicting solubilities of crystalline compounds in binary solvent systems. The solubility of theophylline in mixed solvents consisting of dioxane and water was determined at 25 +/- 0.1 degrees. The solubilities across this range of polar solvents were back-calculated using a technique involving an interaction energy term, W. This parameter is regressed against a polynomial expression in delta 1, the solubility parameter for the mixed solvents. Except for the end-points, solubilities were predicted within less than 12% and with considerably better accuracy in most cases. The new approach modifies the well-known Hildebrand solubility equation to make it applicable to polar systems. Although the method may be used with solutes in pure solvents, its greatest application appears to be the prediction of drug solubility in binary solvent mixtures.

Mathematics↗

Solubility parameter, specific molar cohesion, and the solubility of ethylene oxide in polymers.

The polarity of polymers is commonly characterized by their solubility parameter to describe their interaction with small molecules or by their specific molar cohesion to describe interchain attraction. A linear relation between these two parameters is demonstrated. Ethylene oxide (EO) is used to sterilize containers and devices containing plastics or elastomers. The solubility parameter concept is applicable to the sorption of EO by such polymers provided crystallinity and rubbery/glassy state are taken into account. The delta value of EO, calculated from the temperature dependence of its vapour pressure, is 10.8 (cal/cm3)1/2. The highest EO solubility is in polyvinyl chloride and polycarbonate, whose solubility parameters match that of EO closely. The solubility in other polymers decreases as their solubility parameters diverge increasingly from 10.8. At comparable delta values, polymers in the rubbery state dissolve 6000 to 8000 ppm EO more than polymers in the glassy state. EO solubility in the amorphous fraction of polymers above their glass transition temperatures ranges from 20 800 ppm for plasticized polyvinyl chloride (delta = 9.2) to 800 ppm for polytetrafluorethylene (delta = 6.2).

Ethylene Oxide↗

The estimation of solubility in binary solvents: application of the reduced 3-suffix solubility equation to ethanol-water mixtures.

The reduced 3-suffix solubility equation (R3SSE) is applied to the characterization of solubility in the ethanol-water system. The data needed are the solubility of the compound in each of the pure solvents and at one ethanol-water composition. This composition has been estimated from solubility data to be 0.56 volume fraction of ethanol. The solubility obtained at this volume fraction is used to estimate the ternary solute-solvent interaction constant, C2. The R3SSE, with the C2 thus obtained, predicts the mixed solvent solubilities of the compounds tested, as accurately as that obtained from several volume fractions. The superiority of the R3SSE over two related equations--a simple second-degree polynomial equation and a simplified form of the R3SSE which neglects contributions to solubility from the solvent mixture--is also demonstrated for a number of solutes.

Caffeine↗

Soluble L-selectin attenuates tumor necrosis factor-alpha-mediated leukocyte adherence and vascular permeability: a protective role for elevated soluble L-selectin in sepsis.

OBJECTIVE: We have previously demonstrated that leukocyte delivery to remote sites is decreased in sepsis and that increased concentrations of soluble L-selectin are, in part, responsible for this finding. Given that leukocytes have been implicated in the pathogenesis of vascular leakage, we hypothesized that the elevated soluble L-selectin concentrations in sepsis may translate into decreased inflammation-mediated leukocyte-endothelial cell interactions and vascular leakage at these sites. DESIGN: Prospective, controlled animal study. SETTING: Surgical research laboratory in a university hospital. SUBJECTS: Swiss white male mice weighing 25-35 g. INTERVENTIONS: Mice were randomized to one of three study groups: intracremaster tumor necrosis factor-alpha with subsequent intravenous bicarbonate buffered solution; intracremaster tumor necrosis factor-alpha with intravenous soluble L-selectin (10 microg/mL); and intracremaster bicarbonate buffered solution with intravenous bicarbonate buffered solution. The cremaster muscle was prepared for both light and fluorescence intravital microscopy 2 hrs after intracremaster injection, and fluorescein isothiocyanate-labeled albumin was injected intravenously. Leukocyte-endothelial interactions (rolling flux, rolling velocity, and adherence) were counted off-line. Postcapillary venule leakage was determined by the permeability index (perivenular/intravenular fluorescence) after intravenous injection of fluorescent albumin. MEASUREMENTS AND MAIN RESULTS: Soluble L-selectin significantly attenuated tumor necrosis factor-alpha-mediated increases in leukocyte adherence and vascular leakage. Leukocyte rolling velocity was restored to baseline with soluble L-selectin; however, rolling flux was not altered. Blood pressure, shear rate, and leukocyte counts did not differ between groups. CONCLUSIONS: Soluble L-selectin decreases local inflammation-mediated leukocyte adherence and vascular leakage in vivo. The increased concentrations of soluble L-selectin in sepsis may represent a protective mechanism by which the host attempts to diminish the deleterious systemic effects of activated leukocytes during sepsis.

Animals↗

A cosolvency model to predict solubility of drugs at several temperatures from a limited number of solubility measurements.

A cosolvency model to predict the solubility of drugs at several temperatures was derived from the excess free energy model of Williams and Amidon. The solubility of oxolinic acid, an antibacterial drug, was measured in aqueous (water+ethanol) and non-aqueous (ethanol+ethyl acetate) mixtures at several temperatures (20, 30, 35, 40 degrees C). Oxolinic acid displays a solubility maximum in each solvent mixture at solubility parameter values of 32 and 22 MPa(1/2). The temperature and heat of fusion were determined from differential scanning calorimetry. The solvent mixtures do not produce any solid phase change during the solubility experiments. The experimental results and those from the literature were employed to examine the accuracy and prediction capability of the proposed model. An equation was obtained to represent the drug solubility changes with cosolvent concentration and temperature. The model was also tested using a small number of experimental solubilities at 20 and 40 degrees C showing reasonably accurate predictions. This is important in pharmaceutics because it save experiments that are often expensive and time consuming.

Algorithms↗

17 Beta-hydroxysteroid dehydrogenases in human breast tissues: purification and characterization of soluble enzymes and the distribution of particulate and soluble forms in adipose, non-adipose and tumour tissues.

17 Beta-Hydroxysteroid dehydrogenase (17 beta-HSD) is present in multiple forms in human breast tissue. One soluble form, with a molecular weight of approximately 35 kDa, was purified to near homogeneity from whole normal breast tissue. This form catalysed the oxidation of oestradiol and the reduction of oestrone, with NADP+ and NADPH as the preferred coenzymes. Three other soluble forms with higher molecular weights (in the range 50-80 kDa) were isolated. They catalysed the oxidation of oestradiol but not the reduction of oestrone, and all of them had properties very different from those of the low molecular weight enzyme. Activities of 17 beta-HSD were measured in particulate and soluble fractions from normal breast adipose and non-adipose tissues, and from breast tumours obtained from post-menopausal women, in the oxidative direction with NAD+ and NADP+ as coenzymes and in the reductive direction with NADH and NADPH as coenzymes. Particulate fractions from tumours had much higher oxidative and reductive activities than those from normal tissues. Soluble fractions from tumours had higher oxidative activities than those from the normal tissues but similar reductive activities. The major soluble form of 17 beta-HSD in adipose tissue was the 35 kDa enzyme which had both oxidative and reductive activities. In contrast, the majority of the soluble activity in non-adipose tissue was due to enzymes, with molecular weights in the range 50-80 kDa, which had oxidative activity only. The soluble fractions of tumours, like those of non-adipose tissue, contained enzymes with molecular weights in the range 50-80 kDa. In addition, they contained a 35 kDa enzyme with properties different from those of the enzyme with the same molecular weight present in adipose tissue.

17-Hydroxysteroid Dehydrogenases↗

Different daily blood glucose control and free insulin levels during treatment with mixtures of soluble and lente or soluble and NPH semisynthetic human insulins.

To compare daily blood glucose and free-insulin profiles after the administration of two different mixtures of semisynthetic human insulins (soluble + lente or soluble + NPH), 8 well-controlled insulin-dependent diabetic patients with identical basal blood glucose levels were studied. At the beginning of the first daily period of study, each subject was connected to an Artificial Pancreas to achieve a standard blood glucose (100 mg/dl); after at least 4 hours of normoglycemia, feed-back control was interrupted and the insulin mixture injected, at 8 p.m. and 8 a.m., at the dose previously optimised but always in the ratio 1:2 (1/3 rapid-acting + 2/3 intermediate-acting insulin). Blood glucose and free-insulin were then monitored for a 24-hour period, starting from 8 p.m. The same observation was repeated for each patient a few days later, only changing the intermediate-acting insulin. After dinner (8.30 p.m.) and after breakfast (8.30 a.m.) mean blood glucose was lower with soluble + NPH mixture, while early in the morning and in the late afternoon better glycaemic control was achieved with soluble + lente. F-IRI showed an almost specular behaviour: lower values soon after mixture injection and higher levels 8-12 hours later were observed with soluble + lente than with soluble + NPH. These data indicate that, at the ratio 1:2, the mixture of short-acting with lente HM insulin differs from the one with NPH not only for a lower activity of soluble insulin but also for a stronger and more prolonged effect of the intermediate preparation. This difference should be carefully taken into account in clinical practice.

Adult↗

Lipid-soluble and water-soluble antioxidant activities of the avian intestinal mucosa at different sites along the intestinal tract.

The antioxidant capacity of the avian intestinal mucosa is potentially important in protecting the gut wall from the harmful actions of reactive oxygen species originating from the diet, mucosal metabolism and the inflammatory response to enteric microbes. To assess this capacity, we determined the total lipid-soluble and water-soluble antioxidant activities of mucosal extracts, using tissue from different parts of the intestinal tract of the chicken. The lipid-soluble antioxidants, vitamin E and carotenoids, were also measured in the same samples. Total lipid-soluble antioxidant activity was highest in mucosa from the duodenum followed by the jejunum, with much lower activities in the ileum, ceca and colon. Total water-soluble antioxidant activity of the mucosa was at least an order of magnitude greater than the lipid-soluble activity under the assay conditions and did not differ significantly among the different parts of the intestinal tract. High concentrations of vitamin E were present in the mucosa of the duodenum and jejunum, with a trend to lower levels in the ileum and ceca, and significantly less in the colon. Similarly, the mucosa of the duodenum and jejunum contained the highest concentrations of carotenoids, with much lower levels in the ileum and colon. The different isoforms of vitamin E were absorbed from the digesta by the mucosa without any major selectivity. However, the liver was greatly enriched with alpha-tocopherol over the other isoforms, indicating a high degree of discrimination by this tissue. The results indicate major differences in the relative contributions of lipid- and water-soluble antioxidants in the mucosa along the different parts of the intestinal tract, most likely reflecting the sites of vitamin E and carotenoid absorption.

Animals↗

Reversibly soluble biocatalyst: optimization of trypsin coupling to Eudragit S-100 and biocatalyst activity in soluble and precipitated forms.

Eudragit S-100, a copolymer of methacrylic acid and methyl methacrylate is soluble at pH above 5 and insoluble at pH below 4.5. pH-dependent solubility of the polymer is used for the development of reversibly soluble biocatalyst, which combines the advantages of both soluble and immobilized biocatalysts. Activity of trypsin, covalently coupled to Eudragit S-100, was improved by protecting the active site of the enzyme with benzamidine and removing the noncovalently bound proteins with Triton X-100 in 0.15 M Tris buffer (pH 7.6). Accurate choice of coupling conditions combined with proper washing protocol produced highly active enzyme-polymer conjugate with no noncovalently bound protein. Two conjugates with 100-fold difference in the content of trypsin coupled to Eudragit S-100 were studied when the preparations were in soluble and precipitated forms. The K(m)values of the soluble enzyme to the lower molecular weight substrate was less than that of the free enzyme, whereas that to the higher molecular weight substrate was closer to that of the free enzyme. Activities of the soluble and precipitated immobilized trypsin with higher molecular weight substrate were completely inhibited by soy bean trypsin inhibitor, whereas complete inhibition with soy bean trypsin inhibitor was never achieved with lower molecular weight substrate, indicating reduced access of high-molecular weight substrate/inhibitor to some of the catalytically active enzyme molecules in trypsin-Eudragit conjugate.

Journal Article↗

Only the large soluble form of preadipocyte factor-1 (Pref-1), but not the small soluble and membrane forms, inhibits adipocyte differentiation: role of alternative splicing.

We originally identified preadipocyte factor-1 (Pref-1) as an inhibitor of adipogenesis by the fact that constitutive expression of full-length Pref-1A inhibits differentiation of 3T3-L1 cells into adipocytes. Subsequently, we found that the membrane form of Pref-1 is proteolytically processed at two sites in the extracellular domain, resulting in the larger (50 kDa) and smaller (25 kDa) soluble forms. A specific form(s) of Pref-1, which is active in inhibiting adipocyte differentiation, has not been elucidated. Here, various artificial constructs and alternative-splicing variants of Pref-1 were stably transfected into 3T3-L1 cells, or conditioned media from COS cells transfected with the various forms were added into differentiating 3T3-L1 cells. Judging by Oil Red O staining for lipid accumulation and expression of adipocyte markers, we determined that, unlike the full-length Pref-1A and the constructed large soluble form, the artificial membrane form of Pref-1 lacking the processing site proximal to the membrane was not effective in inhibiting adipogenesis. Furthermore, conditioned media from COS cells transfected with the construct containing only the first three epidermal growth factor repeats, corresponding to the small soluble form, was not effective in inhibiting adipocyte differentiation. Of the four alternative-splicing products, Pref-1A and Pref-1B, which generate both large and small soluble forms, inhibited adipogenesis, whereas Pref-1C and Pref-1D, which lack the processing site proximal to the membrane and therefore generate only the smaller soluble form, did not show any effect. We conclude that only the large soluble form, and not the transmembrane or the small soluble form, of Pref-1 is biologically active and that alternative splicing therefore determines Pref-1 function in adipocyte differentiation.

3T3 Cells↗

Zinc partitions IGFs from soluble IGF binding proteins (IGFBP)-5, but not soluble IGFBP-4, to myoblast IGF type 1 receptors.

Zinc (Zn(2+)), a multifunctional micronutrient, was recently shown to lower the affinity of cell-associated insulin-like growth factor (IGF) binding protein (IGFBP)-3 and IGFBP-5 for both IGF-I and IGF-II, but to increase the affinity of the cell surface type 1 IGF receptor (IGF-1R) for the same two ligands. However, there is a need for data concerning the effects of Zn(2+) on soluble IGFBPs and the type 2 IGF receptor (IGF-2R). In the current work, we demonstrate that Zn(2+) affects the affinity of IGFBP-5 secreted by myoblasts but not IGFBP-4. Zn(2+), at physiological levels, depressed binding of both IGF-I and IGF-II to IGFBP-5, affecting (125)I-IGF-I more than (125)I-IGF-II. Both (125)I-IGF-I and (125)I-IGF-II bound to high and low affinity sites on IGFBP-5. Zn(2+) converted the high affinity binding sites of IGFBP-5 into low affinity binding sites. An IGF-I analog, (125)I-R(3)-IGF-I, did not bind to the soluble murine IGFBP-5. Zn(2+) also decreased the affinity of the IGF-2R on L6 myoblasts. In contrast, Zn(2+) increased IGF-I, IGF-II and R(3)-IGF-I binding to the IGF-1R by increasing ligand binding affinity on both P(2)A(2a)-LISN and L6 myoblasts. Soluble IGFBP-5 and IGFBP-4 depressed the binding of (125)I-IGF-I and (125)I-IGF-II to the IGF-1R, but did not affect binding of (125)I-R(3)-IGF-I. By depressing the association of the IGFs with soluble IGFBP-5, Zn(2+) partitioned (125)I-IGF-I and (125)I-IGF-II from soluble IGFBP-5 onto cell surface IGF-1Rs. This effect is not seen when soluble L6-derived IGFBP-4 is present in extracellular fluids. We introduce a novel mechanism by which the trace micronutrient Zn(2+) may alter IGF distribution, i.e. Zn(2+) acts to increase IGF-1R binding at the expense of IGF binding to soluble IGFBP-5 and the IGF-2R.

Animals↗

Soluble tumor necrosis factor receptor II and soluble cell adhesion molecule 1 as markers of tumor necrosis factor-alpha release in preeclampsia.

BACKGROUND: The purpose of this case-controlled study was to investigate whether plasma concentrations of TNF-receptors I and II and tumor necrosis factor-alpha-induced cell adhesion molecule 1 VCAM-1 could serve as more sensitive markers of tumor necrosis factor-alpha release in preeclamptic women than a direct measurement of circulating tumor necrosis factor-alpha. METHODS: Plasma concentrations of soluble tumor necrosis factor receptor I and II, immunoreactive tumor necrosis factor-a and soluble cell adhesion molecule VCAM-1 were determined in 21 patients with severe proteinuric preeclampsia (23-35 weeks' gestation) and 21 gestational age-matched normotensive controls by enzyme-linked immunoassays. Concentrations of bioactive tumor necrosis factor-alpha were assessed by the WEHI 164 bioassay. Data were statistically evaluated by Wilcoxon's rank sum and sign tests, and Spearman's test was used to evaluate clinical and biochemical correlations. RESULTS: Bioactive tumor necrosis factor-alpha was detected in 19 of 21 preeclamptic and 18 of 21 normotensive women, with no difference in plasma concentrations between both groups. Immunoreactive tumor necrosis factor-alpha, soluble TNF-receptors and soluble cell adhesion molecule VCAM-1 were significantly increased in plasma of preeclamptic patients, and a statistically significant positive correlation was observed between immunoreactive tumor necrosis factor-alpha and TNFRII. In preeclamptic patients a statistically significant negative correlation was observed between TNFRII and platelet count, and between soluble cell adhesion molecule VCAM-1 and birthweight ratio. CONCLUSION: These results show that plasma concentrations of soluble tumor necrosis factor receptor II and soluble cell adhesion molecule VCAM-1 reflect the release of tumor necrosis factor-alpha and provide sensitive markers of excessive release of this cytokine in preeclampsia.

Adolescent↗

Identification of soluble interleukin-1 binding protein in cell-free supernatants. Evidence for soluble interleukin-1 receptor.

This study describes the identification and characterization of a soluble interleukin-1 (IL-1) binding protein in the conditioned media from Raji human B-lymphoma cells. The soluble IL-1 binding material was isolated by IL-1 affinity chromatography, and treatment with trypsin decreased its ability to bind to IL-1 demonstrating its protein nature. The soluble IL-1 binding protein was specific for IL-1 and was able to discriminate between Il-1 alpha and IL-1 beta in a manner analogous to the membrane-bound Raji IL-1 receptor. The specificity of the IL-1 binding protein was further established in two ways. 1) Cell-free supernatants from Raji "receptor-negative" cells did not contain any IL-1 binding protein, thus ruling out nonspecific interactions between IL-1 and a serum or other protein present in the conditioned medium; and 2) the soluble binding protein inhibited IL-1 binding to Raji cells in a dose-dependent manner. Scatchard analysis of IL-1 beta binding showed the dissociation constant (KD) to be 5.1 nM for the soluble IL-1 binding protein compared with 0.8 nM for the membrane-bound IL-1 receptor. Gel chromatography of the soluble binding protein yielded a major peak of IL-1 binding activity with a molecular mass of 35-45 kDa. The characteristics of the soluble IL-1 binding protein described above are consistent with those of the extracellular binding domain of the membrane-bound Raji IL-1 receptor.

Cell Line↗

Soluble microbial products (SMP) and soluble extracellular polymeric substances (EPS) from wastewater sludge.

Laspidou and Rittmann (Water Research 36:2711-2720, 2002) proposed that the soluble extracellular polymeric substances (EPS) are identical to soluble microbial products (SMP) in sludge liquor. In this paper, we compared the physicochemical characteristics of the SMP and soluble EPS from original and aerobically or anaerobically digested wastewater sludge. The surface charges, particle sizes, residual turbidities of polyaluminum chloride (PACl) coagulated supernatant, and chemical compositions of the SMP and soluble EPS containing suspensions were used as comparison index. Experimental results revealed that the particles in SMP and soluble EPS fractions extracted from original wastewater sludge, before and after digestion, were not identical in all physicochemical characteristics herein measured. The current test cannot support the proposal by Laspidou and Rittmann (Water Research 36:2711-2720, 2002) that SMP is identical to the soluble EPS from a wastewater sludge.

Aerobiosis↗

Soluble tumor necrosis factor receptors and soluble interleukin-6 receptor in fetal and maternal sera, coelomic and amniotic fluids in normal and pre-eclamptic pregnancies.

The aim of this study was (a) to measure soluble tumor necrosis factor receptors (sTNF-Rs) and soluble interleukin-6 receptor (sIL-6-R) in coelomic and amniotic fluids, cord and maternal sera in pregnancy and labor, (b) to examine whether the changes in concentrations of biologically active TNF and IL-6 are related to changes in their soluble receptors, and (c) to determine if levels of soluble receptors in pre-eclamptic disorders differ from normal pregnancies at delivery. Materials collected from 206 women during pregnancy and at delivery were analyzed for soluble receptors by enzyme-linked immunosorbent assay (ELISA). All receptors were present in higher concentrations in coelomic than in the corresponding amniotic fluid. Concentrations increased in amniotic fluid from first to second trimester. The level of sIL-6-R then remained unchanged to term, but there was a decrease in the sTNF-Rs which might account for the simultaneous appearance of bioactive TNF. Labor did not affect the concentration of any receptor in amniotic fluid. In maternal serum, sTNF-Rs increased with gestational age and labor in parallel with IL-6. The origin and physiological importance of these soluble receptors are still unknown. In pre-eclamptic disorders p55 sTNF-R was elevated in maternal serum before initiation of labor compared to normal pregnancy.

Adolescent↗