Soluble Adhesion Molecules sICAM-1 Research Articles

Functional activity of the oral endothelium in persons, with chronic periodontitis during treatment with plasmolifting

Chronic periodontitis as an osteoimmune disease of the oral cavity is accompanied by a change in the functional activity of endotheliocytes. Moreover, abnormal vascularization exacerbates periodontal inflammation, as it promotes the transmigration of a larger number of immunocompetent cells, the influx of inflammatory mediators and cytokines.The aim of our work was to study the functional activity of the endothelium of the vessels of the oral cavity in persons suffering from chronic periodontitis in the treatment of plasmolifting.Materials and methods. Under observation were 30 patients diagnosed with chronic generalized periodontitis of moderate severity at the age of 35 (32.50; 40.00) years, with no severe somatic pathology (main group). The comparison group included 20 people aged 38 (34.00; 45.00) years with no inflammatory diseases in the oral cavity. All patients underwent local anti-inflammatory therapy and sanitation of periodontal pockets, correction of occlusal contacts, curettage, plasma lifting. Oral fluid concentration of soluble adhesion molecules ICAM-1 and VCAM-1, endothelin-1, qualitative and quantitative composition of microflora were determined.Results. After the treatment with plasmolifting, a noticeable relief of the activity of the inflammatory process was observed. In patients with chronic periodontitis, Porphyromonas gingivalis was found in 100 % of cases in a titer of 5.73 (4.9; 6.7) lg (gEq/sample), in 62.5 % – Prevotella intermedia in a titer of 4.5 (3.0; 5.5) lg (gEq/sample). Against the background of therapy, decrease of the occurrence of the microorganism and of the number of microorganisms was observed. The concentration of the soluble form of VCAM-1 in the oral fluid of patients with chronic periodontitis exceeded the values of the control group by 38.3 times (p = 0.000001), and ICAM-1 – by 18.1 times (p = 0.00001). Against the background of plasmolifting therapy, the level of the studied substances decreased, but exceeded the control values by 25.2 and 6.4 times, respectively. The content of endothelin in the oral fluid in patients with periodontitis exceeded the values of healthy individuals by 40.7 % (p = 0.003), during therapy its values decreased, but did not reach the level of healthy volunteers (p = 0.04).

Diagnostic and prognostic value of assessment of soluble adhesion molecules sICAM-1 and sVCAM-1 in septic patients

The review is devoted to the assessment of use of cell adhesion molecules including intercellular adhesion molecule type 1 (ICAM-1) and vascular cell adhesion molecule type 1 (VCAM-1) as additional laboratory markers for severity assessment and as predictors of outcome in septic patients. One of the very important pathogenetic components of this state is known to be endothelium activation replaced by its dysfunction. The level of expression of these molecules on endothelial cell membrane affects leukocyte migration from the vessels to surrounding tissues. Besides, a number of cell adhesion molecules are expressed on immunocompetent cells that influences the development of immune response (both innate and acquired). The main characteristics of ICAM-1 and VCAM-1 are presented, including the possibility of soluble forms formation (sICAM-1, sVCAM-1) due to shedding of cell membrane induced by proteolytic enzymes. The results of literature analysis demonstrate that in sepsis the serum content of sICAM-1 and sVCAM-1 is significantly higher than in healthy subjects. In most cases their level is higher than in patients with other critical states (such as severe infectious inflammatory processes, myocardial infarction, stroke, burns, etc.) that according to some authors allows their using for differential diagnosis of sepsis and other critical states. There is no consensus on correlation with disease severity (sepsis, severe sepsis, septic shock), presence of multiple organ failure and its prediction, and lethal outcomes. Results inconsistency most probably can be explained by differences in study design. Nevertheless, continuing studies in this direction is considered perspective.

Potential biomarkers in patients with systemic sclerosis.

Reduced capillary density is considered the hallmark of systemic sclerosis (SSc) leads to tissue hypoxia, a condition that usually induces angiogenesis. The objective of our study is to investigate mediators regulating angiogenesis in SSc and to correlate their levels with serological and clinical parameters. vascular endothelial growth factor, fibroblast growth factor-2, endostatin, thrombospondin-1 and soluble vascular cell and intracellular adhesion molecules (sICAM-1 and sVCAM-1) were measured in sera of SSc and normal subjects by enzyme-linked immunosorbent assay. Among the pro- and anti-angiogenic mediators, endostatin was significantly higher in SSc than in the control subjects. Out of the proteases involved in endostatin production, elastase but not cathepsin-L, was significantly increased in SSc patients. The soluble adhesion molecules sICAM-1 and sVCAM-1 were significantly increased and they occur in parallel. sICAM-1, but not sVCAM-1 positively correlates with the inflammatory markers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Endostatin, elastase and the soluble adhesion molecules (sICAM-1 and sVCAM-1) are potentially involved in the pathogenesis of SSc. Moreover, the significant correlation observed between sICAM-1 and CRP and ESR indicates that sICAM-1 might be a useful biomarker of the inflammatory state of the disease.

The 5A apolipoprotein A-I (apoA-I) mimetic peptide ameliorates experimental colitis by regulating monocyte infiltration.

New therapies for inflammatory bowel disease (IBD) are highly desirable. As apolipoprotein (apo)A-I mimetic peptides are beneficial in several animal models of inflammation, we hypothesized that they might be effective at inhibiting murine colitis. Daily injections of 5A peptide, a synthetic bihelical apoA-I mimetic dissolved in PBS, or PBS alone were administered to C57BL/6 mice fed 3% (w v(-1) ) dextran sodium sulfate (DSS) in drinking water or healthy controls. Daily treatment with 5A peptide potently restricted DSS-induced inflammation, as indicated by improved disease activity indices and colon histology, as well as decreased intestinal tissue myeloperoxidase levels and plasma TNFα and IL-6 concentrations. Additionally, plasma levels of monocyte chemoattractant protein-1 and the monocyte expression of adhesion-mediating molecule CD11b were down-regulated, pro-inflammatory CD11b(+) /Ly6c(high) monocytes were decreased, and the number of intestinal monocytes was reduced in 5A peptide-treated animals as determined by intravital macrophage-related peptide-8/14-directed fluorescence-mediated tomography and post-mortem immunhistochemical F4/80 staining. Intravital fluorescence microscopy of colonic microvasculature demonstrated inhibitory effects of 5A peptide on leukocyte adhesion accompanied by reduced plasma levels of the soluble adhesion molecule sICAM-1. In vitro 5A peptide reduced monocyte adhesion and transmigration in TNFα-stimulated monolayers of human intestinal microvascular endothelial cells. Increased susceptibility to DSS-induced inflammation was noted in apoA-I(-/-) mice. The 5A peptide is effective at ameliorating murine colitis by preventing intestinal monocyte infiltration and activation. These findings point to apoA-I mimetics as a potential treatment approach for IBD.

The Systemic Immune Network in Recent Onset Type 1 Diabetes: Central Role of Interleukin-1 Receptor Antagonist (DIATOR Trial)

BackgroundThe hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics.Methods and FindingsAll patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18–39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25–0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex.ConclusionsIn patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only mediator which correlates (positively) with residual beta cell function.Trial registrationClinicalTrials.gov registration number: NCT00974740

Abstract 19596: Endothelial Acyl-CoA Synthetase 1 is not Required for Saturated Fatty Acid- Mediated Inflammatory and Apoptotic Effects

Saturated fatty acids, such as palmitic (C16:0) and stearic acid (C18:0), cause detrimental effects in endothelial cells (ECs) that might contribute to macrophage accumulation in adipose tissue and the vascular wall in states of obesity and insulin resistance. Fatty acids require conversion into acyl-CoA derivatives to exert most biological effects, a reaction catalyzed by acyl-CoA synthetases (ACSL). We hypothesized that endothelial deficiency of ACSL1, an ACSL isoform mediating inflammatory effects in myeloid cells, would protect from detrimental effects of saturated fatty acids in vitro and saturated fat feeding in vivo. Mouse microvascular CD45-negative-CD31-positive endothelial cells (MMECs) were isolated from lungs or hearts by fluorescence activated cell sorting. In these cells and in bovine aortic ECs (BAECs), saturated fatty acids caused JNK activation, ER stress, and apoptosis, along with increased inflammatory activation, as measured by an increase in the release of the soluble adhesion molecules sICAM-1 (p&lt;0.01), and sVCAM-1 (p&lt;0.01), as well as release of the chemokine CCL2 (p&lt;0.05). In order to evaluate the role of endogenous ACSL1 in ECs, a conditional endothelial Acsl1-deficient mouse model was generated. Acsl1-deficient MMECs had significantly decreased beta-oxidation as measured by decreased acid soluble metabolite production (WT 393.1 ± 25.6, KO 270.5 ± 16.3 cpm/µg protein; p&lt;0.05). However, conditional endothelial ACSL1-deficiency did not protect against the inflammatory or apoptotic effects of saturated fatty acids in vitro, nor did it protect insulin resistant mice fed a saturated fatty acid-rich diet from epididymal adipose tissue accumulation of macrophages or increased aortic adhesion molecule expression. Conversely, forced Acsl1 overexpression in BAECs exacerbated the effects of saturated fatty acids on apoptosis and ER stress, in part through increased JNK activation. In conclusion, forced overexpression of Acsl1 can exacerbate some effects of saturated fatty acids; however, endogenous ACSL1 is not required for pro-inflammatory or pro-apoptotic responses of ECs to saturated fatty acids.

Prognostic significance of adhesion molecules (sICAM-1, sVCAM-1) and VEGF in colorectal cancer patients

IntroductionAdhesion molecules take part in the interaction between host cells and cancer cells. In the current study the relationship between the soluble adhesion molecules sICAM-1 and sVCAM-1 and proangiogenic factor VEGF in colorectal cancer progression were measured. Materials and methodsThe study group consisted of 46 patients with colorectal carcinoma (classified due to TNM classification) and 40 controls. sICAM-1, sVCAM-1 and VEGF plasma concentration were measured by enzyme-linked immunosorbent assay (ELISA). ResultsAll measured parameters levels were increased significantly in patients with colorectal cancer in comparison to controls (p<0.001). sICAM-1, sVCAM-1 and VEGF increased significantly due to colorectal cancer progression. There was a positive correlation between sICAM-1 and sVCAM-1 in all study groups. ConclusionsOur results demonstrated in CRC patients significantly increased levels of soluble adhesion molecules (VCAM-1 and sICAM-1) and angiogenic factor (VEGF) as compared to control group. The dynamics of these molecules showed the growing tendency along with tumor size and metastasis formation.

The Effect of Atorvastatin Treatment on Lipid Profile and Adhesion Molecule Levels in Hypercholesterolemic Patients: Relation to Low-Density Lipoprotein Receptor Gene Polymorphism

Inflammation has been indicated to play a major role in the development of atherosclerosis. The beneficial effect of statins has been suggested to be related to their anti-inflammatory properties. We have studied plasma levels of soluble adhesion molecules in patients with hypercholesterolemia before and after 3 months of treatment with atorvastatin and evaluated possible relations to the mutations in low-density lipoprotein receptor (LDLR) gene. In patients with no LDLR gene polymorphism (group A), lower baseline levels of total cholesterol and LDL cholesterol were found than in patients with LDLR gene polymorphism (group B). The soluble adhesion molecules sICAM-1, sE-selectin and sP-selectin, but not sVCAM-1 and sL-selectin, were higher in group B than in group A. sICAM-1 levels decreased in group A by 7% (p = 0.007) and in group B by 21% (p = 0.039), whereas levels of sVCAM-1 decreased in group A by 12% (p = 0.001) and in group B patients by 19% (p = 0.039). Atorvastatin did not change sE-selectin nor sP-selectin levels in group A. However, in group B, the treatment reduced E-selectin and sP-selectin levels by 39% (p = 0.007) and 24% (p = 0.007), respectively. Atorvastatin attenuates the inflammatory reaction in hypercholesterolemic patients, but in patients with LDLR gene polymorphism, this effect is more profound.

Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and their association with clinical outcome, troponin T and C-reactive protein in patients with acute coronary syndromes

Objectives: The aim of this study was to compare concentrations of soluble intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) in patients with coronary artery disease and healthy control and to evaluate the usefulness of the inflammatory markers as predictors of adverse prognosis in patients with acute coronary syndromes (ACS). Design and methods: ELISA was used to measure sICAM-1 and sVCAM-1 levels in 75 patients with ACS, 36 patients with stable angina pectoris (SAP) and 25 healthy subjects. hsCRP was measured with immunoturbidimetric assay, cardiac troponin T—with electrochemiluminescence immunoassay. Results: All soluble ICAM-1 and VCAM-1 significantly discriminated between patients with ACS and SAP ( p = 0.014 and 0.05, respectively) and control subjects ( p < 0.001 and 0.05). During the 6-month follow-up of the patients with ACS, there were 28 major cardiac events (37.3%). The odds ratio associated with the highest value of sVCAM-1 was 4.62 (95% CI 1.8–11.4, p = 0.0009) without adjustment and remained significantly elevated after adjustment for cTnT (RR 3.93, 1.5–10, p = 0.04) and hsCRP (RR 2.22, 0.8–5.7, p = 0.05). In contrast, an elevated level of sICAM-1 was not associated with future coronary risk after adjustment for cTnT and hsCRP. Conclusions: In patients with acute coronary syndromes, VCAM-1 serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers.

Marcadores inflamatórios intracoronarianos após intervenções coronarianas percutâneas

To analyze intracoronary release of inflammatory markers (IM) after percutaneous coronary interventions (PCI) and compare their concentrations concerning the type of PCI used (rotablator vs. balloon angioplasty). Twenty-two patients with average age of 60 +/- 11.9 years old, 12 of male sex, with stable coronary disease, submitted to elective treatment of a single coronary lesion, using rotablator (N = 11) or balloon pre-dilatation (N = 11) for stent implant were randomized. Samples were collected at aorta root and coronary sinus, immediately before and 15 minutes after intervention. All dosages were made before stent implant, and the cytokines TNF-a, IL-6 and IL-1 and the soluble adhesion molecules ICAM-1, E-selectin and P-selectin were analyzed by using ELISA method. TNF-a and IL-6 concentrations increased after PCI, respectively from 9.5 +/- 1.5 pg/ml to 9.9 +/- 1.8 pg/ml (p = 0.017) and from 6.0 +/- 2.4 pg/ml to 6.9 +/- 3.0 pg/ml (p < 0.001). There was no significant changes in IL-1, ICAM-1 and P-selectin, and a decrease in E-selectin concentrations after the procedures (52.0 +/- 17.5 ng/ml to 49.3 +/- 18.7 ng/ml; p = 0.009) was observed. There were no significant differences between IM concentrations after PCI, concerning the type of procedure used. At the early period, post-percutaneous coronary interventions, an increase of intracoronary concentrations of TNF-a and IL-6, and absence of significant difference between concentrations of inflammatory markers released in coronary flow through rotablator and balloon angioplasty were observed.

Markers for endothelial activation during open heart surgery

Background Reliable markers for endothelial activation are needed when studying biocompatibility of cardiopulmonary bypass. Methods Blood samples from 21 patients undergoing combined valve and coronary artery bypass surgery were collected before anesthesia (T1), after re-transfusion of blood from the heart-lung machine (T2), and on the first postoperative morning (T3). Concentrations of soluble markers were determined using sandwich enzyme-linked immunoadsorbent assay for sICAM-1, sVCAM-1, and sE-selectin. The sera were also used to stimulate human umbilical vein endothelial cells (HUVEC) in culture for 6 hours, in which activation was measured using cell enzyme immunoassay for mICAM-1 and mVCAM-1. Results The concentrations of sICAM-1 and sVCAM-1 increased during both measurement intervals ( p < 0.05). The sICAM-1 T1 was 311.0 ng/mL (range, 271.0 to 350.7 ng/mL); the sICAM-1 T2 was 341.6 ng/mL (range, 322.0 to 422.0 ng/mL), and the sICAM-1 T3 was 400.2 ng/mL (range, 348.0 to 556.4 ng/mL; the sVCAM-1 T1 was 607.5 ng/mL (range, 497.8 to 813.8 ng/mL), the sVCAM-1 T2 was 755.3 ng/mL (range, 660.6 to 834.4 ng/mL), and the sVCAM-1 T3 was 1149.0 ng/mL (946.0 to 1406.0 ng/mL); whereas the sE-selectin increased from T1 to T3 ( p < 0.01). Both the mICAM-1 ( p < 0.002) and the mVCAM-1 ( p < 0.005) increased on the human umbilical vein endothelial cells in culture after stimulation with the patient sera. The amounts of soluble markers in vivo were not correlated with the degree of endothelial activation in vitro, but were correlated with various operative variables including age, medication, and time of aortic cross-clamping. Conclusions Endothelial cells were activated during cardiopulmonary bypass. The soluble adhesion molecules sICAM-1, sVCAM-1, and sE-selectin displayed different kinetics, rendering it difficult to determine a simple expression for the degree of endothelial cell activation. Clinically, sVCAM-1 seemed to be the best-suited marker for endothelial cell activation, because it was only associated with aortic cross-clamping and heparin and protamine doses, and it also showed the largest numerical changes.

Effects of occupational exposure to styrene on expression of adhesion molecule on leukocytes.

Styrene is an indispensable chemical extensively used in plastic and synthetic rubber industries. Styrene is known to produce various types of hepatotoxic, neurotoxic, and genotoxic effects. Styrene may be immunotoxic by both direct and indirect mechanisms. Measurement of adhesion molecules is a new tool for the investigation of immune system modulation. The aim of this study was to evaluate the association of the expression of the adhesion molecules CD11a, CD11b, CD18, CD54, CD49d, and CD62-L in white blood cells and levels of soluble adhesion molecules ICAM-1 and L-selectin in serum with occupational exposure to styrene. Analyses by flow cytometry revealed elevated levels of most of the assessed adhesion molecules on surfaces of lymphocytes, monocytes, and granulocytes. Expression of the adhesion receptor antigens CD11a on lymphocytes, CD11b on monocytes, and CD18 on granulocytes were unaffected. Workers exposed to styrene had decreased concentrations of sICAM-1 and no changes in concentrations of sL-selectin. Styrene exposure appears to increase activation of the immune system and alter leukocyte adherence. This interaction is a critical first step in immune stimulation and leukocyte-endothelial interaction.

Serum levels of soluble adhesion molecules ICAM-1, VCAM-1 and E-selectin in patients with Wegener's granulomatosis

Objective: To examine the role of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble E-selectin (sE-selectin) in the pathogenesis of Wegener's granulomatosis (WG) and the values of measuring serum levels of these soluble adhesion molecules for monitoring disease activity during follow-up, a total of 24 serum samples from 16 patients with WG were studied. Methods: The serum concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1 and sE-selectin) and cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6)) of patients with WG were measured by ELISA. Results: The serum levels of sICAM-1 were significantly elevated in active WG and correlated with disease activity. At the time of relapse, a significant increase of sICAM-1 was also observed. The serum levels of TNF-α and IL-6 were also significantly elevated in active WG. Conclusion: These findings suggest that sICAM-1 plays an important role in the pathogenesis of WG and may be used as an additional parameter of disease activity.

Mononuclear cell adhesion to collagen ex vivo is related to pulse pressure in elderly subjects

Mononuclear cells and platelets are intimately involved in the pathogenesis and complications of cardiovascular disease. Platelet activation has been reported in hypertension, though the activation-state of monocytes has received less attention. In this study the adhesiveness of monocytes and platelets was assessed and any relationship between the adhesive properties of these cellular elements and plasma levels of soluble adhesion molecules and blood pressure parameters determined. Fifty six elderly volunteers, of whom 32 were classified hypertensive (daytime SBP≥135 mmHg), underwent 24 h blood pressure monitoring, assessment of monocyte and platelet adhesion and measurement of the plasma soluble adhesion molecules ICAM-1, L-selectin, E-selectin and vWF. In the elderly hypertensive subjects, monocyte adhesion to collagen coated ( P<0.05) and tissue culture plastic microwells ( P<0.05) was significantly elevated and circulating levels of soluble ICAM-1 ( P<0.01) and soluble E-selectin ( P<0.05) were significantly raised compared to their normotensive counterparts. A significant correlation was found to exist between monocyte adhesion to collagen and daytime pulse pressure ( r=0.39, P<0.01) and also between plasma levels of soluble E-selectin and clinic DBP ( r=0.40, P<0.001). The increased monocyte adhesion witnessed in hypertensive subjects and with increasing pulse pressure may contribute to the increased risk of cardiovascular disease in hypertension. Whether this increased adhesiveness is a property of the monocytes, or reflects endothelial cell activation, remains to be determined.

Serum Levels of Soluble Adhesion Molecules in Chronic Renal Failure and Dialysis Patients

Besides cell-bound adhesion molecules, which are of fundamental importance to a large number of physiological and pathological processes, soluble forms of adhesion molecules have been detected in the circulating blood in recent years. Circulating soluble adhesion molecules appear to be biologically active, and raised levels have been reported in a variety of disorders. In the present study, we used ELISA to measure the serum levels of four soluble adhesion molecules in 23 undialyzed patients with chronic renal failure (CRF), 13 patients on continuous ambulatory peritoneal dialysis (CAPD), 17 on chronic hemodialysis (HD) and 18 healthy controls having a similar mean and distribution of ages. The investigated soluble (s) molecules included intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), sE-selectin and sP-selectin. sICAM-1 was found to be elevated in patients with CRF (p < 0.05), on CAPD (p < 0.02) and HD (p < 0.0001) compared with the controls but levels did not differ between the three patient groups. The higher sVCAM-1 values found in CRF (p < 0.02), CAPD (p < 0.05) and HD (p < 0.0001) as compared to controls again failed to differentiate the three groups of patients. Soluble E-selectin was also raised in the three groups (p < 0.0001) with no difference between them. Increased sP-selectin was found in CRF (p < 0.05), CAPD (p < 0.02) and in HD patients (p < 0.0001) compared to controls, and levels in HD were significantly higher (p < 0.02) than in CRF patients. Predialysis serum molecule levels did not differ between HD patients treated with cuprophan or with polyacrylonitrile dialyzers. HD sessions with both dialyzers had no effect on sICAM-1, while a decrease (p < 0.02) in sP-selectin was found after dialysis with cuprophan. In undialyzed patients with CRF, regression analysis showed a strong linear correlation between serum creatinine and serum levels of each soluble molecule. These results demonstrate that serum levels of soluble adhesion molecules ICAM-1, VCAM-1, E-selectin and P-selectin are elevated in both undialyzed patients with CRF and patients on CAPD or HD. The elevated serum levels of these proteins probably reflect inadequate clearance as well as enhanced synthesis/release.

The release of soluble adhesion molecules ICAM-1 and E-selectin after acute myocardial infarction and following coronary angioplasty

Endothelial cells express surface adhesion molecules for leukocytes in response to myocardial ischaemia. These molecules may be released into plasma by activated cells and be detectable in soluble form. Samples were collected from the peripheral vein of 14 consecutive patients with acute myocardial infarction (AMI) at the time of admission, 6 h, and 1 and 5 days post-admission. Additionally, samples were drawn from the coronary sinus ostium and peripheral artery of seven patients undergoing coronary angioplasty (PTCA) before and after the first balloon inflation. We measured the plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sELAM-1). In patients with AMI plasma levels of sICAM-1 exceeded those observed in age and sex-matched healthy subjects, (mean±SEM; 220.6±18 ng/ml) at all the time intervals assessed (358.9±24.5; 330.9±24.4; 379.4±39.7 and 366.8±47.5 ng/ml, respectively, p<0.01). sELAM-1 levels, however, were normal on admission, increased at 6 h to 52.7±3.8 ng/ml, p<0.05, and at day 1 (56.0±4.6 ng/ml) before decreasing to normal levels on the fifth day. After brief myocardial ischaemia occurring during PTCA, an increased level of sICAM-1 was observed following balloon deflation in the coronary sinus (329.2±20 ng/ml; p<0.05) as compared to the subjects undergoing coronary angiography, but not in the peripheral artery. sELAM-1 levels remained unchanged during angioplasty. Thus, soluble adhesion molecules expressed by activated endothelial cells are released into peripheral blood during both AMI and brief myocardial ischaemia and measurement of such molecules may prove useful for monitoring vascular endothelium activation following myocardial ischaemia/necrosis.

Elevated Levels of Circulating Soluble Adhesion Molecules in Patients With Nonrheumatic Aortic Stenosis

Increased serum levels of soluble adhesion molecules are found in various disorders of inflammatory or immunologic etiology. We found elevated levels of the soluble adhesion molecules ICAM-1, VCAM-1, and E-selectin in patients with nonrheumatic aortic stenosis, suggesting that inflammation may be important in the pathogenesis of this condition, which is generally believed to be degenerative.

Neutrophilic dermal infiltrates in granulocytopenic patients with acute leukemia

Acute febrile neutrophilic dermatosis (AFND, Sweet's syndrome) is clinically characterized by fever, neutrophilic leukocytosis, and tender dermal plaques. Histological examination typically reveals infiltration of the dermis by neutrophils. In three patients (2 female, 1 male, 54-59 years) with acute leukemia (2 myelogenous, 1 lymphoblastic) dermal plaques developed during febrile episodes in chemotherapy-induced pancytopenia. The clinical appearance was compatible with AFND. The diagnosis was substantiated by skin biopsies which showed dense neutrophilic dermal infiltrates without leukemic cells. Leukocytoclastic vasculitis was considered as differential diagnosis. Plasma levels of soluble adhesion molecules ICAM-1, VCAM-1, and E-selectin regulating leukocyte transendothelial migration were in the normal range. Systemic glucocorticoids were avoided because of the high risk of infection during prolonged bone marrow aplasia. The lesions were treated with topical steroids and resolved without scarring within 1-5 weeks. AFND has been reported in association with acute leukemia at normal or elevated white blood cell counts. Although implausible from a pathophysiological point of view, similar neutrophilic dermal infiltrates were found in three patients during chemotherapy-induced pancytopenia with white blood cell counts distinctly below 1 x 10(9)/l.

Low dose versus medium dose UV-A1 treatment in severe atopic eczema.

Twenty-two patients with severe atopic eczema were included in a therapy study with UV-A1 (wavelengths > 340 nm) treatment. The patients were divided into two dose groups, each consisting of 11 patients. One group received 10 J/cm2 and the other 50 J/cm2 five times a week for 3 consecutive weeks. No topical or systemical steroids or antihistamines were allowed. Using the SCORAD index as a measure of disease activity before onset of therapy and after 10 and 15 treatments, we observed a significant improvement in both dose groups after 15 treatments (10 J/cm2: p < 0.05, 50 J/cm2: p < 0.005). After 10 treatments only the improvement in the 50 J/cm2 group was significant (p < 0.005); the difference between the two dose groups was significant (p < 0.05). The clinical efficacy of treatment was reflected neither by a decrease of serum IgE nor by a decrease of elevated serum levels of soluble adhesion molecules sICAM-1 and sELAM-1 in the two dose groups. In contrast, a marked but not significant decrease of serum ECP could be observed in the 50 J/cm2 group only. We conclude from these and other published data that although 10 J/cm2 UV-A1 has a limited effect on patients with severe atopic eczema, higher doses are of higher efficiency in the treatment of this condition.

Elevated Serum Levels of Soluble Adhesion Molecules ICAM-1 and ELAM-1 in Patients with Severe Atopic Eczema and Influence of UVA1 Treatment

ICAM-1 is known to be strongly expressed on keratinocytes in lesional atopic eczema correlating with the degree of inflammation. ELAM-1 was found to be expressed on dermal vascular endothelium in lesional atopic eczematous skin. The present study was performed to investigate whether elevated serum levels of soluble forms of these molecules are detectable in patients with severe atopic eczema and whether these parameters could be useful markers for disease activity. Serum levels of soluble ICAM-1 (sICAM-1) and ELAM-1 (sELAM-1) were measured by ELISA in 18 patients with severe atopic eczema before and after UVA1 therapy. Before onset of treatment, serum sICAM-1 (565 +/- 99 ng/ml) and sELAM-1 (89.7 +/- 29.9 ng/ml) levels were significantly (p < 0.001) elevated compared to 22 healthy control persons (296 +/- 46 and 48.8 +/- 22.7 ng/ml). After achievement of significant clinical improvement after 3 weeks of UVA1 therapy, there was neither a decrease in serum sICAM-1 nor in sELAM-1 levels. The posttherapeutic serum sICAM-1 and sELAM-1 values remained elevated (p < 0.001) above the normal range. Based on these data we suggest that (1) serum sICAM-1 and sELAM-1 are elevated in patients with severe atopic eczema, (2) sICAM-1 does not decrease together with reduction of ICAM-1-positive keratinocytes in atopic eczema following clinical improvement and might therefore be mainly of a different origin, i.e. leukocytes/endothelial cells, and that (3) sICAM-1 and sELAM-1 seem not to be suitable markers of actual disease activity in severe atopic eczema.