A novel inflammatory marker for extensive ulcerative colitis; Endocan.

BACKGROUND & AIMS: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by mucosal inflammation. Endocan, a proteoglycan secreted by endothelial cells in response to inflammatory cytokines, has been reported to be overexpressed in inflammatory conditions. In this study, we aimed to evaluate the utility of endocan level in determining the extent and severity of disease in patients with ulcerative colitis and to determine whether it can be a candidate marker for noninvasive evaluation and monitoring since there is not enough data in the literature. MATERIALS AND METHODS: Sixty-five people were included in the study, including thirty-five with ulcerative colitis and thirty in the control group. Patients with first diagnosed ulcerative colitis clinically, endoscopically, and histopathologically, without any treatment, and with normal liver and kidney tests were included in the study. Endoscopic scoring of all patients was performed according to the Mayo endoscopic scoring (MES) system. Blood samples for CRP (C-reactive protein) and endocan were taken from the patients simultaneously. RESULTS: There was a significant statistical difference between all patients with ulcerative colitis and the control group in both endocan level and CRP level (p < 0.001). There was a statistically significant difference between endocan levels and CRP levels between the left-distal group and pancolitis (diffuse colitis) patients, but there was no statistical difference between age and MES. CONCLUSION: Serum endocan level can be useful in determining the extent of ulcerative colitis and planning treatment.

Mineralocorticoid receptor-antagonism prevents COVID-19-dependent glycocalyx damage.

Proinflammatory cytokines target vascular endothelial cells during COVID-19 infections. In particular, the endothelial glycocalyx (eGC), a proteoglycan-rich layer on top of endothelial cells, was identified as a vulnerable, vasoprotective structure during infections. Thus, eGC damage can be seen as a hallmark in the development of endothelial dysfunction and inflammatory processes. Using sera derived from patients suffering from COVID-19, we could demonstrate that the eGC became progressively worse in relation to disease severity (mild vs severe course) and in correlation to IL-6 levels. This could be prevented by administering low doses of spironolactone, a well-known and highly specific aldosterone receptor antagonist. Our results confirm that SARS-CoV-2 infections cause eGC damage and endothelial dysfunction and we outline the underlying mechanisms and suggest potential therapeutic options.

Increasing circulating ESM-1 and adhesion molecules are associated with earlystage atherosclerosis in OSA patients:A cross-sectional study.

BACKGROUND: There are increasing evidences for a direct relationship between the vascular system and obstructive sleep apnea (OSA). The aim of this study was to investigate the relationship between circulating endothelial cell specific molecule-1 (ESM-1), adhesion molecules and subclinical atherosclerosis in patients with OSA. METHODS: This was a cross-sectional study in which 161 patients with OSA and 56 controls were recruited. Demographic data, biochemical and polysomnography parameters were collected. We used a powerful high-throughput Multiplex Immunobead Assay technique to simultaneously test plasm levels of ESM-1, P-selectin, E-selectin, L-selectin, inter-cellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Carotid intima-media thickness (CIMT) were measured as parameters of vascular endothelial dysfunction and early atherosclerosis. RESULTS: Increasing circulating levels of ESM-1, P-selectin, E-selectin, L-selectin, ICAM-1 and VCAM-1 were found increased in patients with OSA (all P < 0.001). Furthermore, OSA patients exhibited increased CIMT than controls (P < 0.05). Multivariate linear analysis indicated that elevated ESM-1, P-Selectin, E-selectin, and L-selectin levels were associated with AHI (all P < 0.05). Moreover, multivariate analysis showed that increasing ESM-1, VCAM-1, P-Selectin, and L-selectin were significantly associated with thick CIMT in OSA patients (all P < 0.05). CONCLUSIONS: Increased circulating ESM-1 and adhesion molecules associated with thick CIMT in OSA, which is a marker of subclinical atherosclerosis. Strict attention to monitor circulating ESM-1 and adhesion molecules is necessary for early detection of subclinical atherosclerosis in OSA patients.

ß-1,3-d-Glucan and Galactomannan as Biomarkers for the Detection of Invasive Geotrichum and Magnusiomyces Infections: a Retrospective Evaluation.

Magnusiomyces and Geotrichum species are ascomycetous yeasts that can cause potentially life-threatening invasive fungal infections commonly referred to as geotrichosis. In this study, we aimed to estimate the incidence and mortality of these infections in a German tertiary care center. Furthermore, we evaluated the suitability of the fungal biomarkers galactomannan (GM) and ß-1,3-d-glucan (BDG), which are both recommended as surrogate markers for Magnusiomyces capitatus infection by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) joint clinical guidelines for the diagnosis and management of rare invasive yeast infections for detection of invasive geotrichosis. Cases meeting the inclusion criteria for invasive Magnusiomyces/Geotrichum infection were retrospectively identified. Serum samples and culture supernatants were analyzed with two commercially available fungal antigen tests (Platelia Aspergillus Ag EIA and Wako ß-glucan test). For a control cohort, outpatient samples sent for lues testing were included. Thirty-eight cases of Magnusiomyces/Geotrichum infection were identified over an 11-year observation period. In the majority of cases, the fungus was isolated from intra-abdominal specimens of patients with a history of abdominal surgery/procedures (n = 32). All cases of fungemia occurred exclusively in haemato-oncologic patients (n = 14). Thirty-day survival was 42% in the fungemia and 43% in the intra-abdominal geotrichosis group. Serum samples were available for 23 patients (14 bloodstream and nine intra-abdominal infections). While BDG sensitivity was 65%, none of the sera was GM positive. This finding was supported by in vitro experiments analyzing fungal culture supernatants: M. capitatus secretes significant amounts of BDG but not GM. Specificity was 96% for BDG and 100% for GM. Magnusiomyces and Geotrichum infections are not limited to haemato-oncologic patients. Contrasting the current ESCMID/ECMM recommendation, our results indicate that GM is no suitable biomarker for the diagnosis of Magnusiomyces infection. Contrarily, BDG sensitivity is comparable to that of candidemia.

Serum Expression of ESM-1, HMWA, and AGEs and Its Relationship with Disease Severity in Patients with Gestational Hypertension.

OBJECTIVE: The research is to investigate the expression and the relationship between serum endothelial cell-specific molecular molecule-1 (ESM-1), high molecular weight adiponectin (HMWA), and late glycosylation terminal product (AGEs) in patients with gestational hypertension. METHODS: 75 patients with pregnant hypertension who were treated in our hospital from June 2019 to June 2020 were selected as the case group, and 70 healthy pregnant women with pregnancy examination at the same period in our hospital were selected as the control group to analyze the changes in serum ESM-1, HMWA, and AGEs levels and the correlation with the degree of illness and their predictive value. RESULTS: Serum ESM-1 and AGEs were significantly higher in the case group than in the control group. Serum HMWA was significantly lower than that in the control group (P < 0.05). The gestational hypertensive serum ESM-1 and AGEs was significantly lower than in patients with mild preeclampsia and severe preeclampsia. Serum HMWA was significantly higher than in patients with mild preeclampsia and severe preeclampsia. Serum ESM-1 and AGEs of mild preeclampsia were significantly lower than in patients with severe preeclampsia. Serum HMWA was significantly higher than in patients with severe preeclampsia (P < 0.05). The result of correlation analysis shows a positive correlation between serum ESM-1 and AGEs (P < 0.05). A negative correlation was observed between HMWA and the degree of illness (P < 0.05). CONCLUSION: Serum ESM-1, HMWA, and AGEs are abnormally expressed in gestational hypertension, are closely related to the degree of condition, and have important clinical significance for condition control.

Overfeeding Saturated Fat Increases LDL (Low-Density Lipoprotein) Aggregation Susceptibility While Overfeeding Unsaturated Fat Decreases Proteoglycan-Binding of Lipoproteins.

Objective: We recently showed that measurement of the susceptibility of LDL (low-density lipoprotein) to aggregation is an independent predictor of cardiovascular events. We now wished to compare effects of overfeeding different dietary macronutrients on LDL aggregation, proteoglycan-binding of plasma lipoproteins, and on the concentration of oxidized LDL in plasma, 3 in vitro parameters consistent with increased atherogenicity. Approach and Results: The participants (36 subjects; age, 48+/-10 years; body mass index, 30.9+/-6.2 kg/m2) were randomized to consume an extra 1000 kcal/day of either unsaturated fat, saturated fat, or simple sugars (CARB) for 3 weeks. We measured plasma proatherogenic properties (susceptibility of LDL to aggregation, proteoglycan-binding, oxidized LDL) and concentrations and composition of plasma lipoproteins using nuclear magnetic resonance spectroscopy, and in LDL using liquid chromatography mass spectrometry, before and after the overfeeding diets. LDL aggregation increased in the saturated fat but not the other groups. This change was associated with increased sphingolipid and saturated triacylglycerols in LDL and in plasma and reduction of clusterin on LDL particles. Proteoglycan binding of plasma lipoproteins decreased in the unsaturated fat group relative to the baseline diet. Lipoprotein properties remained unchanged in the CARB group. Conclusions: The type of fat during 3 weeks of overfeeding is an important determinant of the characteristics and functional properties of plasma lipoproteins in humans.

Serum endocan levels in multiple sclerosis relapse and remission.

OBJECTIVE: Endocan has been defined as an important marker of inflammatory diseases, vascular and endothelial injury, tumour progression, cell adhesion and angiogenesis. In our study, we compared the serum endocan, C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) levels of relapsing-remitting multiple sclerosis (RRMS) patients in remission and in relapse. PATIENTS AND METHODS: This study included 53 RRMS remission patients, 30 RRMS relapse/post-relapse patients and 44 healthy volunteers. Blood samples were collected once from RRMS patients in remission and from the control group, and twice from RRMS relapse patients: once when relapsing and another 1 month after relapse. The endocan, CRP and NLR levels of the RRMS patients measured while in relapse, 1 month after relapse and while in remission were compared to those of the control group. The studied parameters were compared with the disease duration, relapse frequency, Expanded Disability Status Scale (EDSS) score, applied treatment and lesion burden assessed using magnetic resonance imaging (MRI). RESULTS: The endocan, CRP and NLR levels were significantly higher in the RRMS group than in the control group (p < 0.05). The serum endocan levels were found to be significantly higher in the RRMS relapse group than in the post-relapse and control groups (p < 0.05). There were no significant correlations between the disease duration, EDSS score, relapse frequency and lesion burden on MRI and the endocan, CRP and NLR values (p > 0.05). According to the correlation analysis, there was a statistically strong positive relationship between the MRI lesion localisation and the EDSS score, disease duration and relapse frequency (p < 0.001). CONCLUSIONS: Endocan increase is a marker of the endothelial injury that develops secondary to the inflammatory process in MS patients. It can thus be considered a moderately good indicator of relapse.

Diagnostic and Prognostic Value of Serum Endocan Levels in Patients With COVID-19.

We aimed to evaluate whether there was a relationship between endocan (human endothelial cell-specific molecule-1) levels and disease prognosis in patients who presented to the emergency department with coronavirus disease 2019 (COVID-19). A total of 60 patients with COVID-19 who were hospitalized from the emergency department to clinical wards and a control group consisting of healthy adult individuals (n = 28), were included in the study. The majority (93.3%) of the patients were discharged after recovery; 6.7% died. The median endocan value was 243.5 ng/mL in the patient group versus 201.5 ng/mL in the control group (P = .002). The median endocan level was 240.5 ng/mL in those discharged with recovery and 558 ng/mL in those who died (P = .001). There was no significant relationship in hospitalization duration, sex, tomography findings, and clinical outcomes. A 202 ng/mL serum endocan level had 86.7% sensitivity and 50% specificity for COVID-19. Serum endocan levels may be a useful biomarker both for the diagnosis of COVID-19 and to predict mortality.

Candida Administration in Bilateral Nephrectomy Mice Elevates Serum (1→3)-ß-D-glucan That Enhances Systemic Inflammation Through Energy Augmentation in Macrophages.

Systemic inflammation, from gut translocation of organismal molecules, might worsen uremic complications in acute kidney injury (AKI). The monitoring of gut permeability integrity and/or organismal molecules in AKI might be clinically beneficial. Due to the less prominence of Candida albicans in human intestine compared with mouse gut, C. albicans were orally administered in bilateral nephrectomy (BiN) mice. Gut dysbiosis, using microbiome analysis, and gut permeability defect (gut leakage), which was determined by fluorescein isothiocyanate-dextran and intestinal tight-junction immunofluorescent staining, in mice with BiN-Candida was more severe than BiN without Candida. Additionally, profound gut leakage in BiN-Candida also resulted in gut translocation of lipopolysaccharide (LPS) and (1→3)-ß-D-glucan (BG), the organismal components from gut contents, that induced more severe systemic inflammation than BiN without Candida. The co-presentation of LPS and BG in mouse serum enhanced inflammatory responses. As such, LPS with Whole Glucan Particle (WGP, a representative BG) induced more severe macrophage responses than LPS alone as determined by supernatant cytokines and gene expression of downstream signals (NFκB, Malt-1 and Syk). Meanwhile, WGP alone did not induced the responses. In parallel, WGP (with or without LPS), but not LPS alone, accelerated macrophage ATP production (extracellular flux analysis) through the upregulation of genes in mitochondria and glycolysis pathway (using RNA sequencing analysis), without the induction of cell activities. These data indicated a WGP pre-conditioning effect on cell energy augmentation. In conclusion, Candida in BiN mice accelerated gut translocation of BG that augmented cell energy status and enhanced pro-inflammatory macrophage responses. Hence, gut fungi and BG were associated with the enhanced systemic inflammation in acute uremia.

Is serum endocan a sensitive biomarker for early recurrence of hepatocellular carcinoma after radiofrequency ablation?

BACKGROUND AND AIM OF THE WORK: Hepatocellular cancer (HCC) is one of the common liver cancers and considered to be the sixth most commonly occurring cancer in the world and the second leading cause of death among cancer patients. More recent studies on HCC showed that the elevated serum endocan level was a predictive factor of recurrence after radiofrequency ablation. The aim of this study is to evaluate the serum endocan level as a prognostic biomarker for recurrence of HCC after percutaneous radiofrequency ablation. PATIENTS AND METHODS: Analytic-prospective study was carried out in Suez Canal University Hospitals. The study was carried out on 80 patients classified into three groups: group 1 (control group) consisted of 20 apparently healthy persons; group 2 consisted of 20 patients with liver cirrhosis; and group 3 consisted of 40 treatment-naive HCC patients who were prepared for radiofrequency ablation. All HCC patients (who were confirmed to have complete ablation after RF) were followed up by using triphasic abdominal CT, serum AFP and serum endocan assessment at 3 and 6 months after radiofrequency ablation. RESULTS: Our study revealed a high level of serum endocan in the HCC group with a statistically significant difference (<0.001) between the three groups. HCC patients had a higher level of serum endocan (6.2 ± 2.25) followed by an liver cirrhosis group (2.0 ± 1.29) and then the control group (1.0 ± 0.3). The serum endocan level had a positive correlation with recurrence of HCC (P < 0.0001). There was a positive correlation between serum endocan and serum alanine transferase (P = 0.02), and a positive correlation between serum endocan and the number of tumors (P = 0.01). CONCLUSION: Serum endocan is considered as a prognostic biomarker for tumor recurrence in HCC patients after radiofrequency ablation.

Tsukushi and TSKU genotype in obesity and related metabolic disorders.

PURPOSE: Whether Tsukushi (TSK) can protect against high-fat diet (HFD)-induced obesity and improve glucose metabolism remains controversial. Serum levels of TSK in the population have not been reported until now. We assessed the association among TSK level, TSKU genotype, and metabolic traits in humans. METHODS: Associations between serum TSK levels and metabolic traits were assessed in 144 Han Chinese individuals. Loci in the TSKU gene region were further genotyped in 11,022 individuals. The association between the loci and serum TSK level was evaluated using the additive genetic model. The association between the loci and their metabolic traits in humans were also verified. RESULTS: Lower TSK levels were observed in obese subjects than in control subjects (median and interquartile range 17.78:12.07-23.28 vs. 23.81:12.54-34.56, P < 0.05). However, in obese subjects, TSK was positively associated with BMI (ß ± SE: 0.63 ± 0.31, P = 0.049), visceral fat area (ß ± SE: 12.15 ± 5.94, P = 0.011), and deterioration of glucose metabolism. We found that rs11236956 was associated with TSK level in obese subjects (ß 95% CI 0.17, 0.07-0.26; P = 0.0007). There was also a significant association between rs11236956 and metabolic traits in our population. CONCLUSIONS: Our findings showed that serum TSK levels were associated with metabolic disorders in obese subjects. We also identified rs11236956 to be associated with serum TSK levels in obese subjects and with metabolic disorders in the total population.

Endocan: A Novel Predictor of Endothelial Dysfunction in Silent Brain Infarction.

Silent brain infarction (SBI) has been considered as a subclinical risk factor for symptomatic possible future stroke. We investigated the association between serum inflammatory markers and SBI. Patients (n = 54) diagnosed with SBI as the study group and 52 individuals as the control group were included in this study. Silent brain infarction is defined as a hyperintense lesion that was ≥3 mm in 1 dimension on fluid-attenuated inversion recovery T2-weighted magnetic resonance image, if the patient had normal neurological examination or had an abnormality that was not consistent with the brain lesion locations, after being evaluated by a neurologist. Serum endocan levels (P = .036) and high-sensitivity C-reactive protein (hsCRP; P = .022) were significantly higher in patients with SBI than the controls. Pentraxin 3, erythrocyte sedimentation rate, white blood count, lymphocyte, monocyte, neutrophil, low-density lipoprotein, and triglyceride levels were not significantly different when comparing the groups with and without SBI. There was a significant correlation (r = -0.196; P = .16) between hsCRP and endocan levels in the SBI group. Endocan, a novel biomarker of endothelial pathology, was significantly increased in patients with SBI and may be useful to predict the future risk of stroke.

Diagnostic accuracy of the 1,3-beta-D-glucan test and lactate dehydrogenase for pneumocystis pneumonia in non-HIV patients.

We evaluated the serum levels of (1-3)-beta-D-glucan (BG) and lactate dehydrogenase (LDH) as a tool to support pneumocystis pneumonia (PCP) diagnostic procedures in non-HIV patients. We retrospectively collected non-HIV (human immunodeficiency virus) patients presenting clinical features of PCP between April 1st, 2013, and December 31st, 2018. A total of 225 included patients were tested for Pneumocystis jirovecii by polymerase chain reaction (PCR) and methenamine silver staining. Based on different exclusion criteria, 179 cases were included in the BG group, and 196 cases were included in the LDH group. In each group, cases with positive immunofluorescence (IF) microscopy and PCR were considered proven PCP, while cases with only positive PCR were considered probable PCP. Fifty patients with negative IF and PCR results and proven to be non-PCP infection were chosen randomly as the control group. The cut-off levels of BG and LDH to distinguish non-PCP from probable PCP were 110 pg/mL and 296 U/L with 88% sensitivity and 86% specificity, and 66% sensitivity and 88% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven PCP were 285.8 pg/mL and 379 U/L with 92% sensitivity and 96% specificity, and 85% sensitivity and 77% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven/probable PCP were 144.1 pg/mL and 363 U/L with 90% sensitivity, 86% specificity and 80% sensitivity, 76% specificity respectively. BG and LDH are reliable indicators for detecting P. jirovecii infection in HIV-uninfected immunocompromised patients.

The combination of soluble tumor necrosis factor receptor type 1 and fibroblast growth factor 21 exhibits better prediction of renal outcomes in patients with type 2 diabetes mellitus.

PURPOSE: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. METHODS: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. RESULTS: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. CONCLUSION: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.

Prospective comparison of (1,3)-beta-D-glucan detection using colorimetric and turbidimetric assays for diagnosing invasive fungal disease.

Serum (1→3)-ß-D-glucan (BDG), an pan fungal antigen, is detected in some invasive fungal diseases (IFDs). We compared two commercial kits, the Fungitell assay (FA) (colorimetric) and the Wako assay (WA) (turbidimetric) over a 4-month period to prospectively test 171 patients who mainly had hematological conditions (62%) and experienced episodes (n = 175) of suspected invasive fungal infection. Twenty-three episodes due to BDG-producing fungi were diagnosed (pneumocystosis, n = 12; invasive aspergillosis, n = 5; candidemia, n = 3; invasive fusariosis, n = 2; hepato-splenic candidiasis, n = 1).Both assays provided similar areas under the curves (AUC = 0.9). Using the optimized positivity thresholds (≥120 pg/ml for FA and ≥ 4 pg/ml for WA), the sensitivity and specificity were 81.8% (CI95: 61.5-92.7), 94.8% (90.1-97.3) for FA and 81.8% (61.5-92.7), 95.4% (90.9-97.8) for WA. Negative predictive value was 97.3% (93.3-99.0) for both tests. If the manufacturer's positivity threshold (≥11 pg/ml) was applied, the WA sensitivity decreased to 50%. Among 71 patients with bacterial infections, 21.1% were FA-positive and 5.6% were WA-positive (p < 10-2).The WA performed similarly as compared to the FA with an optimized cutoff value. The WA is a single sample test that is clinically relevant when a prompt therapeutic decision is required. LAY SUMMARY: Serum (1→3)-ß-D-glucan testing is dominated by two kits including Fungitell colorimetric assay (FA) and the Wako turbidimetric assay (WA). We compared them prospectively and observed that they both perform similarly when selecting their optimal threshold (≥120 pg/ml for FA and ≥ 4 pg/ml for WA).

Impaired endothelial function irrespective of systemic inflammation or atherosclerosis in mastocytosis.

BACKGROUND: Knowledge on endothelial dysfunction and its relation to atherosclerosis in mastocytosis is limited. OBJECTIVE: To investigate the endothelial function in mastocytosis by flow-mediated dilatation (FMD) and biomarkers related to vascular endothelia and to evaluate its relationship with the presence of subclinical atherosclerosis by carotid intima media thickness (CIMT). METHODS: A total of 49 patients with mastocytosis and 25 healthy controls (HCs) were included. The FMD and CIMT during transthoracic echocardiography biomarkers including endocan, endothelin-1, and vascular endothelial growth factor (VEGF) were measured in the sera of participants. Tumor necrosis factor-alpha, interleukin 6, and high-sensitive C-reactive protein were determined as inflammatory biomarkers. RESULTS: The mean FMD % was lower in the patients than HCs (11.26% ± 5.85% vs 17.84% ± 5.27% P < .001) and was the lowest in the advanced systemic mastocytosis and smoldering systemic mastocytosis group among the patients (P = .03). The median value of VEGF was considerably higher in patients than HCs (73.30 pg/mL; minimum-maximum 32.46-295.29 pg/mL vs 46.64 pg/mL; minimum-maximum, 11.09-99.86 pg/mL; P = .001) and it was the highest in the advanced systemic mastocytosis and smoldering systemic mastocytosis group (P = .01). The FMD was inversely correlated with endocan (r = -0.390; P = .006), endothelin-1 (r = -0.363; P = .01) and VEGF (r = -0.402; P = .004) but there were no correlations between FMD and tumor necrosis factor-alpha, interleukin 6, and high-sensitive C-reactive protein. No differences in CIMT values between patients and HCs and no correlation between CIMT and the biomarkers were observed. CONCLUSION: Endothelial dysfunction in mastocytosis becomes evident with decreased FMD and elevated serum VEGF in the absence of atherosclerosis or systemic inflammation and is related to disease severity.

Development and application of novel immunoassays for eosinophil granule major basic proteins to evaluate eosinophilia and myeloproliferative disorders.

BACKGROUND: During eosinophil differentiation, the granule eosinophil major basic protein 1 (eMBP1) is synthesized as a 32-kDa precursor form, referred to as proMBP1, which is processed into the 14-kDa mature form of eMBP1. The prevalence of these two forms of MBP1 in most pathological conditions remains unknown. OBJECTIVE: To develop the immunoassays that differentiate mature eMBP1 and proMBP1 and apply them to analyze their levels in biological fluids from patients with eosinophilia and hematologic disorders. METHODS: We produced a series of monoclonal antibodies and selected pairs capable of discriminating between the two molecular forms of eMBP1. Radioimmunoassay (RIA) was performed to simultaneously quantitate the levels of mature eMBP1 and proMBP1 in secretions from patients with chronic rhinosinusitis (CRS) and sera from patients with hypereosinophilic syndrome (HES) and other myeloproliferative disorders. RESULTS: The novel immunoassays possessed less than 1% crossreactivity between mature eMBP1 and proMBP1. Mature eMBP1, but not proMBP1, was found in nasal secretions of CRS patients. In contrast, elevated serum levels of mature eMBP1 and proMBP1 were observed in approximately 60% and 90% of HES patients, respectively, with proMBP1 present in greater quantities than mature eMBP1. Patients with several myeloproliferative disorders also showed high serum levels of proMBP1 while mature eMBP1 remained at basal levels. CONCLUSION: The novel immunoassays successfully differentiated mature eMBP1 and proMBP1 in human biological fluids. Further studies addressing the clinical correlates of these assays will help to develop biomarkers to diagnose and monitor patients with eosinophilia and myeloproliferative disorders.

Increased Carotid Intima-Media Thickness and Endothelial Cell-Specific Molecule-1 (Endocan) Levels in Obese Children.

Obesity in children appears to be associated with increased risk of cardiovascular and metabolic diseases later in life. Early development of insulin resistance (IR) may lead to endothelial dysfunction and increased carotid intima-media thickness (cIMT) even in childhood. We compared endothelial cell-specific molecule-1 (endocan) levels in pediatric obese patients with those in healthy controls to determine whether endocan could be used as a biological marker of complications caused by endothelial damage. In 80 obese pubertal children (44 males [M] and 36 females [F], mean age: 12.8 ± 2.5 years), anthropometric measurements, cIMT, endocan levels, and IR indices (homeostasis model assessment of insulin resistance [HOMA-IR]) were evaluated and compared with 80 healthy pubertal patients (42M/38F, mean age: 12.3 ± 3.2 years). High-resolution ultrasound was used to measure the cIMT. Obese children had higher levels of endocan compared with the controls (P < .001). Fasting insulin levels and HOMA-IR were also higher in obese children (P < .001 for both). In addition, obese children had an increased cIMT (P < .001). In obese children, there was a significant correlation between cIMT and HOMA-IR (ß = -1.314, P = .002) and between cIMT and endocan (ß = .483, P = .004). Measuring cIMT and endocan levels (noninvasive investigations) in obese children, together with early preventive measures, could significantly decrease morbidity and mortality in adulthood.