Elevated serum concentrations of S100-A11 and AIF-1 in cervical dysplasia patients.

OBJECTIVE: The aim of this study was to compare TFF3, AIF-1, S100-A11 and DKK1 serum levels in patients with cervical dysplasia, and in healthy female controls. METHODS: The first group included 59 patients with a histological dia-gnosis of precancerous disease CIN 1. The second group included 198 patients with a histological dia-gnosis of precancerous disease CIN 2 or CIN 3. The control group was comprised of 90 patients who underwent elective total hysterectomy for nonmalignant disorders. In all patients, preoperative serum samples were taken and separated; the sera were all stored at -80°C until the analysis for TFF3, AIF-1, S100-A11 and DKK1. RESULTS: The serum levels of S100­A11 (P < 0.0001) and AIF-1 (P < 0.0001) were statistically significantly higher in patients with mild precancerous lesions (CIN 1) than in controls. The levels of TFF3 and DKK1 were not statistically significantly different in patients with CIN 1 and in the control group. The serum levels of S100­A11 (P < 0.0001) and AIF-1 (P < 0.0001) were statistically significantly higher in patients with severe precancerous lesions (CIN 2/3) than in controls. TFF3 and DKK1 levels were not statistically significantly different in patients with CIN 2/3 compared to controls. CONCLUSION: S100-A11 and AIF-1 represent potential bio-markers in patients with cervical dysplasia.

Serum concentrations of S100-A11 and AIF-1 are elevated in cervical cancer patients with lymph node involvement.

OBJECTIVE: The aim of this study was to compare the serum levels of TFF3, AIF-1, S100-A11 and DKK1 in surgically staged patients with cervical cancer, and in healthy female controls. METHODS: In total 85 consecutive patients dia-gnosed at the Department of Obstetrics and Gynecology, University Hospital in Olomouc with cervical cancer undergoing radical hysterectomy or fertility sparing surgery with pelvic lymphadenectomy were included. Ninety patients who underwent elective total hysterectomy for nonmalignant disorder represented a control group. In all patients, preoperative serum samples were taken and separated; the sera were all stored at -80 °C until analysis for TFF3, AIF-1, S100-A11 and DKK1. RESULTS: According to the final histopathological examination, 32 (40.5%) out of 79 cervical cancer patients with microscopically examined lymph nodes were lymph node-positive. S100­A11 (P < 0.0001) and AIF-1 levels (P < 0.0001) were higher in cervical cancer patients than in controls. Furthermore, the serum levels of S100­A11 (P > 0.04) and AIF-1 (P > 0.01) were significantly higher in lymph node-positive patients as compared to lymph node-negative patients. The levels of TFF3 and DKK1 were higher (P < 0.0001) in controls than in cervical cancer patients and were not different in groups with or without nodal involvement.. CONCLUSION: S100-A11 and AIF-1 represent potential bio-markers in patients with cervical cancer. Moreover, the levels of S100-A11 and AIF-1 increase in patients with lymph node  involvement.

Plasma levels and leucocyte RNA expression of adipokines in young patients with coronary artery disease, in metabolic syndrome and healthy controls.

OBJECTIVES: Little is known about the role of adipokines in the pathogenesis of coronary artery disease in young patients. The aims of this study were to compare serum levels of adipokines and expression of adipokines in peripheral blood leukocytes in patients with premature coronary artery disease (CAD), metabolic syndrome and healthy individuals. DESIGN AND METHODS: Sixty-five patients with premature CAD (men 18-45years old and women 18-55years old) formed the study group. The control groups were 75 patients with metabolic syndrome and 50 healthy individuals. For each group, RNA expression in peripheral blood leukocytes was determined for 24 different adipokines and 11 adipokines were examined in serum. RESULTS: In individuals with CAD, serum visfatin levels were significantly higher than in metabolic syndrome and healthy controls (2.3 vs. 1.6 vs. 0.7µg/L, P<0.001) while both omentin-1 (92.9 vs. 587.0 vs. 552.3µg/L, P<0.001) and ZAG2 (45.5 vs. 72.5 vs. 77.1mg/L, P<0.001) levels were lower. The receiver operating curve (ROC) analysis for testing the validity of these adipokines in the diagnosis of CAD compared to control groups provided the following areas under the curve (AUC): omentin-1 AUC 0.97 (cut-off ≤222µg/L), ZAG2 AUC 0.89 (cut-off ≤51.7mg/L) and visfatin AUC 0.74 (cut-off ≥1.0µg/L) (P<0.001 in all cases). Visfatin and omentin-1 serum levels did not differ between the acute phase of myocardial infarction and the chronic phase of CAD. In patients with CAD, we found no significant relation between mRNA expression and adipokine concentration. CONCLUSION: Serum omentin-1, visfatin and ZAG2 could serve as biomarkers of premature CAD in young apparently healthy people.

Measurement of novel adipokine visfatin in young patients with acute myocardial infarction. Clinical testing of a new ELISA.

OBJECTIVES: Adipose tissue produces a number of adipokines that have metabolic effect. Visfatin is a recently discovered adipokine whose concentration in plasma increases in obesity. It is also a proinflammatory mediator that promotes atherosclerosis and plays a role in plaque destabilization. The aim of this study was to evaluate an assay for the determination of visfatin in human plasma and to investigate its clinical relevance as a marker of acute coronary syndrome (ACS) in a young population (Men under 45 y, Women under 55 y). DESIGN AND METHODS: We clinically tested a sandwich ELISA assay in young individuals with acute myocardial infarction (n=36) vs. a control group (n=21). The control sample was a healthy proband without inflammation, hepatic or renal injury and under 55 years of age. RESULTS: Visfatin in plasma was able to differentiate the control group from young patients with acute myocardial infarction (5 vs. 27 ng/L). Visfatin in the plasma of acute myocardial infarction (AMI) probands, correlated in individuals with acute coronary syndrome was related to plasma glucose (r=0.47; P=0.01), type 2 diabetes mellitus (r=0.65; P=0.01), plasma creatinine concentration (r=0.3, P=0.02), hsCRP (r=0.29; P=0.03), BMI values (r=0.18; P=0.04), triglycerides (r=0.5; P=0.01) and NT-proBNP (r=0.21; P=0.04). In healthy subjects, these relations were not found. ROC analysis: visfatin cut-off concentration was 20 ng/L with a sensitivity of 84% and a specificity of 90%. The area under the curve (AUC) of cTNI was 0.96, the AUC of visfatin was 0.96. Thus, there was no difference. CONCLUSION: We conclude that visfatin in serum may be a new independent potential marker of AMI.

Comparison of a new immunoassay and PCR-based method for quantification of microRNAs in whole blood. A pilot methodical study.

BACKGROUND: MicroRNAs (miRNAs) are new generation biomarkers used in oncology, cardiology, metabolic syndrome, obesity or in neurology. miRNAs are short non-coding RNA molecules that regulate gene expression in eukaryotes. AIM: To compare a new commercial method for establishing miRNA (imunoassay) with a commercial kit RT qPCR. METHODS: RNA was isolated from whole blood samples obtained from four healthy volunteers. The isolates were liquated and miRNA-93-5p and miRNA-23a-3p were measured independently with commercial hsa-miR-93-5p miREIA and hsa-miR-23a-3p miREIA, and commercial RT-qPCR kits. RESULTS: Both miRNAs had good analytical characteristics, very good correlation with RT qPCR. The results between immunoassay and RT qPCR did not statistically differ. A method based on ELISA was faster (2 h with ELISA vs. 3 h with qPCR) and had lower CV then a method based on RT qPCR (see more text). CONCLUSION: MicroRNAs from blood or derived fractions are particularly interesting candidates for routine laboratory applications. The immunoassay can be performed on any device that processes the ELISA plates and is therefore available in almost every laboratory.

Omentin-1 levels in patients with premature coronary artery disease, metabolic syndrome and healthy controls. Short communication.

OBJECTIVES: Omentin-1 is an adipokine which could have a protective role against the manifestation of atherosclerosis. Only limited data are available on omentin-1 serum values in patients with premature clinical manifestations of atherosclerosis. DESIGN AND METHODS: We tested omentin-1 in human serum by ELISA method in 61 individuals with a premature manifestation of coronary artery disease (CAD), 40 patients with metabolic syndrome and 40 healthy control subjects. RESULTS: Omentin-1 serum levels were significantly lower in patients with CAD (103.1±62.7 mg/L) compared to metabolic syndrome (668.2±339.6 mg/L) and healthy subjects (623.0±373.5 mg/L) (P < 0.01). In CAD patients, omentin-1 serum levels did not differ between patients sampled in the acute phase of myocardial infarction (n = 28; 110.3±82.4 mg/L) and in the chronic phase several months or years after myocardial infarction (n = 33; 97.0±39.3 mg/L) (P = 0.41). We found a weak positive correlation between omentin-1 and body mass index (r = 0.21, P = 0.014). No significant correlation was found between peak cardiac troponin T and omentin-1 (correlation coefficient r = 0.118, P = 0.406). CONCLUSION: Serum omentin-1 seems to be a useful biomarker of coronary artery disease across the whole age spectrum.

Determination of serum visinin like protein-1 and its potential for the diagnosis of brain injury due to the stroke: a pilot study.

BACKGROUND: The current diagnosis of stroke relies on clinical examination by a physician supplemented by various neuroimaging techniques. A single set or multiple sets of blood biomarkers that could be used in acute settings to diagnosis stroke, differentiate between stroke types, and ideally predict an initial/recurring stroke would be extremely valuable. The diagnosis of stroke is currently hampered by delay due to lack of a suitable tool for rapid, accurate and analytically sensitive biomarker - based testing. There is a clear need for further assay development and clinical validation in this area (acute stroke setting) in order to improve patient outcomes and quality of life. Visinin like protein 1 (VILIP-1) is a newly discovered CNS-abundant protein which has shown promise in experimental studies, for early stroke diagnosis. However, to date there is no clinical study that has measured VILIP-1 in sera as a marker of stroke. AIM: To develop an assay for the determination of VILIP-1 in human serum, and to investigate its clinical relevance as a marker of ischemic stroke. DESIGN AND METHODS: A new sandwich ELISA was developed, introduced and clinically tested. Mean spiking recovery was 98%. The mean recovery for dilution linearity was 93%. The limit of detection of the assay was 0.01 mcg/l; the intraassay and interassay coefficient of variation (CV) were always less than 10%. The study was approved by the Ethics Commission of the Hospital Sternberk, Czech Republic. A total of 17 healthy individuals (9 men and 8 women, age 64.0 ± 13.0) and 16 individuals with ischemic stroke (10 men and 6 women, age 63.0±11.5) were recruited for our study. The criteria of stroke were proposed by the National Czech Standard. All individuals had blood samples drawn, and VILIP-1 analysis and CT and/or MRI were performed. Results. VILIP-1 serum level significantly differentiated healthy subjects from patients with stroke (P<0.01). All individuals with stroke had VILIP-1 serum values higher than > 0.05 mcg/l, healthy had values below this value. The diagnostic efficacy of serum VILIP-1 was very significant (sensitivity 100%, specificity 100% at 0.093 mcg/l VILIP-1 serum values, AUC 1.0 (CI 0.93-1.0, P<0.01), Chi-squared in the frequency table was 33 (P<0.01). CONCLUSION: We have introduced a new analytical tool for the study of VILIP-1. Our results support the hypothesis that serum VILIP-1 may be associated with ischemic stroke. The ELISA VILIP-1 assay offers a new research tool for the diagnosis and pathophysiology of stroke and other CNS diseases.

Collagenous repeat-containing sequence of 26 kDa protein - a newly discovered adipokine - sensu lato - A minireview.

BACKGROUND: Increasing evidence from numerous research studies in internal medicine shows that adipocytes and adipokines are involved in primary inflammatory processes and disease. CORS-26 (collagenous repeat- containing sequence of 26 kDa protein) is a newly discovered adipokine of the C1q/TNF molecular superfamily C1q/TNF-related protein-3 (CTRP-3) secreted, inter alia in murine monocytes and adipocytes and in human adipocytes. Reported recently as a gene product of adipocyte differentiation, it shares structural similarity with the adipocyte, adiponectin. CORS-26 is much less known than other adipocytes such as leptin and resistin. Knowledge of its various functions has clinical and therapeutic implications especially in relation to obesity and the metabolic syndrome. AIMS: This review aims to provide current knowledge of this adipokine. METHODS: Review; sources were scientific biomedical databases Medline/PubMed, BioMedCentral, Google Scholar, Ovid, ProQuest from to 1998 to 2009. CONCLUSION: CORS-26 is an adipokine that regulates the secretion of other adipokines. Its effects on adipokine secretion are most probably independent of PPAR-γ. As CORS-26 up-regulates adiponectin secretion, it may be involved in metabolic and immunologic pathways. The effect of recombinant CORS-26 on insulin signaling in the presence of the metabolic syndrome needs to be investigated to further evaluate the physiological and pathophysiological role of this protein.

Macrophage-inhibitory cytokine-1 (mic-1) in differential diagnosis of dyspnea--a pilot study.

BACKGROUND: Macrophage inhibitory cytokine-1 (MIC-1) has recently been associated with markers of heart function. AIM: This study sought to verify the relationship between markers of heart function (New York Heart Association classification (NYHA)): left ventricle ejection fraction (LVEF), N terminal prohormone of natriuretic peptide B type (NT-proBNP) and MIC-1. Furthermore, the assessment of the usefulness of these markers for differential diagnosis of the myocardial form of dyspnea was explored. METHODS: 124 patients (65 women and 59 men) were examined for dyspnea without signs of acute coronary syndrome. All patients underwent echocardiography (calculation of left ventricle ejection fraction-LVEF), and serum NT-proBNP, proguanylin as well as MIC-1 were determined. 21 healthy individuals were defined as the control group. RESULTS AND DISCUSSION: Patients were divided into two groups: A--individuals with non-cardiogenic form of dyspnea, n=77 and B--individuals with cardiogenic ethiology of dyspnea, n=47. Significant differences between MIC-1 values in individuals with cardiogenic dyspnea (median 2189.6 ng/L) and non-cardiogenic dyspnea (median 232.1 ng/L) were shown. MIC-1 correlated with age, proguanylin, NT-proBNP and negatively with LVEF (P<0.05). The median values of MIC-1 were closely associated with the NYHA classification (P<0.05). Division of the group under study according to the cause of dyspnea revealed a significant difference in MIC-1 (P<0.01). The cut-off of MIC-1>444.5 ng/L showed 100% sensitivity and 89.3% specificity for diagnosing cardiogenic dyspnea. After adjustment for age, gender and NT-proBNP, MIC-1 levels were significantly associated with the cardiogenic type of dyspnea (P<0.05). We also tested the difference in MIC-1 level among the subgroup with the cardiac form of dyspnea (10 individuals suffered from hypertension and 37 patients had no sign of hypertension). Individuals with and without hypertension had no significant difference in MIC-1 level. CONCLUSION: MIC-1 is a new diagnostic marker in the differential diagnosis of dyspnea.

Chemerin is an independent marker of the metabolic syndrome in a Caucasian population--a pilot study.

AIM: Chemerin is a novel adipokine that has been suggested to play an important role in the pathogenesis of the metabolic syndrome. The aim of our study was to evaluate serum chemerin as a marker of the metabolic syndrome and to assess its predictive accuracy in a Caucasian population. METHODS: The study was designed as a cross-sectional study. Anthropometric measurements and serum analyses were done for Body Mass Index, waist circumference, chemerin, insulin, triacylglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, and glucose in 55 non-obese healthy subjects and 181 subjects at risk for the metabolic syndrome. ROC curves were determined and the Chi-squared test was used to analyse the data. RESULTS: Compared with healthy controls, subjects with suspected metabolic syndrome had significantly higher chemerin serum levels (medians: 266.0 vs.192.5 microg/l; P < 0.01). After further chemerin adjustment, the difference between the subgroups persisted. Chemerin serum levels correlated with age (r = 0.23), serum glucose (r = 0.23), HDL-cholesterol (r = -0.19), triacylglycerides (r = 0.22), systolic and diastolic blood pressure (r = 0.40; r = 0.24) and the number of metabolic syndrome risk factors (r = 0.47). At a serum chemerin cut-off level of 240 microg/l, the presence of the metabolic syndrome was diagnosed with 75 % sensitivity and 67 % specificity. CONCLUSION: In conclusion, serum chemerin levels are associated with the characteristics of the metabolic syndrome and could be an independent marker of this disorder in a Caucasian population.