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.

Free plasma metanephrines as a screening test for pheochromocytoma in low-risk patients.

OBJECTIVES: Detection of free plasma metanephrines seems to be the most exact method for biochemical diagnosis of pheochromocytoma, but their diagnostic efficacy in the common low-risk clinical settings is debated. METHODS: A cross-sectional multicentre study including 1260 subjects assessed the diagnostic efficacy of free plasma metanephrine and normetanephrine in low-risk patients screened for resistant or markedly accelerated hypertension, paroxysmal hypertension, 'flushes' and, in a small proportion, for adrenal incidentaloma or genetic predisposition to pheochromocytoma. RESULTS: Pheochromocytoma was identified and verified by histology in 25 subjects (2%), with the diagnosis not confirmed by long-term follow-up or use of imaging techniques in the remaining 1235 individuals. The combined assay of free plasma metanephrines was a highly sensitive (100%) and specific (96.7%) measure, yielding a negative predictive value of 100%. CONCLUSION: The satisfactory diagnostic efficacy of free plasma metanephrines allows their use as a single screening test in cases of suspected pheochromocytoma in the population with a low pretest probability.

Use of glycogen phosphorylase BB measurement with POCT in the diagnosis of acute coronary syndromes. A comparison with the ELISA method.

BACKGROUND: Glycogen Phosphorylase BB (GPBB) is considered an early and specific marker of myocardial necrosis and ischemia. A POCT kit GPBB for diagnostic use has recently been approved. AIM: an evaluation of the correspondence of qualitative POCT GBPP measurements with ELISA test results. MATERIAL AND METHODOLOGY: 20 individuals with non-ST elevation myocardial infarction (non-STEMI) and 20 probands without acute coronary syndrome (ACS) were tested. GPBB (POCT, ELISA) in venous plasma (lithium-heparin) was assayed in all probands. RESULTS: individuals with non-STEMI had significantly higher GPBB ELISA values (32.3 vs. 6.1 microg/l; p < 0.01). GPBB sensitivity and specificity for non-STEMI presence 6 hours after chest pain generation were 100 %. No proband was classified in a different subgroup with POCT of GPBB (positive/negative). GPBB POCT correlate with a non- STEMI diagnosis (chi(2) 36.1; p <0.01). CONCLUSION: GPBB POCT measurement is comparable with ELISA test results. GPBB analysis could expand the diagnostic palette in the first hours after the onset of acute coronary syndrome.

Reg-Ialpha in the diagnosis of acute coronary syndrome--a pilot study.

The commonly used laboratory markers of coronary involvement in subjects with acute coronary syndrome (ACS) are not yet myocardial ischemia-specific and show a late irreversible involvement of the myocardium. A laboratory test has been searched for in order to distinguish persons with myocardial ischemia and typical CAD symptoms to CAD-free individuals. Reg-Ialpha is the product of Reg-I gene which plays a significant role in myocardial regeneration. 38 individuals with suspicion of acute coronary syndrome were tested on admission, after 2 and 6 hours. In all of them cardiac troponin I, myoglobin, C-reactive protein (CRP) and Reg-I alpha were analysed. Our findings did not support the hypothesis that measurement of Reg-Ia maybe the useful marker of myocardial stress.

Our experiences with measurement of new potential biomarkers in the diagnosis of latent forms of myocardial ischemia.

BACKGROUND: The need for a laboratory marker of myocardial ischemia has been alluded to for at least the last decade. AIM: The aim of this study was to evaluate the diagnostic importance of the myosin light chain-1 (MLC-1), clusterin and Reg-Ialpha in patients with suspected myocardial ischemia. METHODS: A group of 176 at high-risk for myocardial ischemia subjects was evaluated and divided into two subgroups using myocardial SPECT (Single Photon Emission Computed Tomography) - individuals with and without signs of myocardial ischemia. Laboratory markers in venous blood were repeatedly examined in all subjects: a) immediately prior to SPECT: C-reactive protein, Haemoglobin, Hematocrite, Lactate, MLC-1, Clusterin, Reg-Ialpha b) at subjective maximum: Hb, Htc, lactate, MLC-1, Clusterin, Reg-Ialpha c) 30 min after stress levels reached their peak: MLC-1, Clusterin, Reg-Ialpha and d) 60 min after peak stress levels: MLC-1, Clusterin, Reg-Ialpha. RESULTS: Patients were divided into subgroups according to their positive and negative SPECT results (positive: n = 37; negative: n = 139). MLC-1 values were different for all 4 blood collections. An increase in MLC-1 > 2.2 mg/l showed 64 % sensitivity and 88 % specificity for the diagnosed presence of myocardial ischemia (AUC 0.81; LR+ 5.9; PPV+ 68 % and NPV- 87 %). There was no significant difference between the groups in terms of Clusterin and Reg-Ialpha for any of the sampling periods. CONCLUSIONS: High diagnostic efficacy of detectable MLC-1 was shown for the diagnosis of latent myocardial ischemia. Measurement of serum Clusterin or Reg-Ialpha did not sufficient for the diagnosis of latent myocardial ischemia.

MCL-1 (myosin light chains-1) in differential diagnosis of dyspnea.

Myosin light chains-1 (MLC-1) have been recently associated with the markers of heart function (NYHA, LVEF, NT-proBNP). Verification of the relationship between markers of heart function (New York Heart Association classification (NYHA), left ventricle ejection fraction determination (LVEF), N terminal prohormone of natriuretic peptide B type BNP (NT-proBNP) and concentrations of myosin light chains-1 (MLC-1) was assessed. Patients examined for dyspnea without signs of acute coronary syndrome. All patients underwent echocardiography (calculation of left ventricle ejection fraction--LVEF) and in the serum of all subjects NT-proBNP (ELEIA) and MLC-1 (ELISA) were determined. In the 38 patients (21 men, 17 women), mean age of 58 years (+/-12 years as 1 SD), a significant negative correlation was found between NT-proBNP and LVEF (r = - 0.47; p = 0.02, Spearman). The median levels of NT pro-BNP were closely associated with NYHA classification (type II--584 ng/l, type III--2792 ng/l, type IV--6400 ng/l; p < 0.05). Individuals with clinical NYHA IV differed significantly in median MLC-1 concentrations from persons with clinical NYHA classification II and III (type II--5.7 ng/l, type III--8.9 ng/l, type IV--17 ng/l; p < 0.05). A significant negative correlation between MLC-1 and LVEF (-0.35; p < 0.03) and significant positive correlations between MLC-1 and NT-proBNP (0.42; p < 0.012) were found. In conclusion MLC-1 cannot be used as a diagnostic marker in differential diagnosis of dyspnea.

The antioxidant acetylcysteine reduces oxidative stress by decreasing level of AOPPs.

Oxidative stress and especially its connection with many diseases has been discussed much recently. Among markers of oxidative stress there appear new and quite specific ones called advanced oxidation protein products (AOPPs). We tried to influence the level of AOPPs by an antioxidant therapy with N-acetylcysteine. Fourteen individuals with many cardiovascular risk factors were examined. All these patients were administered acetylcysteine (NAC) 600 mg/day orally during 20 days. Before starting the therapy we determined AOPP, albumin cobalt binding (ACB), glucose, creatinine, urea, ALT, AST, cholesterol, LDL, HDL and triglycerides values in peripheral venous blood in all individuals. After finishing our intervention we determined AOPP, ACB and glucose level again. Our results show a statistically significant decrease in AOPP levels after 20-day N-acetylcysteine therapy (medians, initially 82.2, at study end 74.3 umol/l, p = 0.039). We demonstrate a significant decrease in AOPP levels after 20-day N-acetylcysteine therapy in dose 600 mg/day.

Application of determined NT-proBNP in physical standardized exercise.

UNLABELLED: Natriuretic peptides can be used as markers of heart failure, its severity and also in the differential diagnosis of dyspnea. Moreover, the dynamics of natriuretic peptides in physical standardized exercise may be used in the assessment of latent heart failure. AIM OF THE STUDY: Can determination of NT-proBNP be used in the diagnosis of exercise-induced ischemia or latent heart failure? 18 probands (10 men, 8 women) under study were risk persons with unspecified ECG, without signs of manifest heart failure. They were subjected to ergometric bike exercises up to the subjective maximum, SPECT myocardium with estimated ejection fraction of the left ventricle at peak ergometric exercise. The following parameters were followed-up: a) before ergometric exercise: NT-proBNP, CRP, TNF-alpha, Hb, Htc, lactate b) at subjective maximum: NT-proBNP, Hb, Htc, lactate c) 30 min after stopping the exercise: NT-proBNP d) 60 min after stopping the exercise: NT-proBNP. The volume blood changes were taken into account (estimation from the dynamics of Htc, Hb with calculation of metabolic changes of NT-proBNP). To evaluate the dynamics of NT-proBNP, the group was divided into subgroups according to the results obtained in ergometric exercises. RESULTS: initial values of NT-proBNP within normal limits (< 59 pmol/l, 500 ng/l) in 94%, the submaximal pulse rate was reached in 94%, ischemic changes in ECG were observed in 59%, typical clinical signs of heart ischemia were recorded in 35%. Signs of heart dysfunction according to SPECT were found in 47% and ischemic symptoms were observed in 43%. In general, the plasmatic volume decreased by 24% at maximal exercise. Lactate concentration in the plasma increased in all cases. Conversion of NT-proBNP into volume blood changes revealed that increased NT-proBNP occurred only in 22%. Differences between NT-proBNP before exercises and at maximal exercise prior and after correction into volume blood changes were statistically insignificant. 30 and 60 min after the exercise, no significant differences were found in NT-proBNP concentrations. Dividing into subgroups according to the results of ergometric exercises, showed no significant differences in NT-proBNP concentrations. Dynamics of NT-proBNP changes during and after ergometric exercises cannot be used for the diagnosis of exercise-induced heart failure. The high stability of NT-proBNP related to physical activity was confirmed.