Acute-phase response and its biomarkers in acute and chronic urticaria.

INTRODUCTION: Since urticaria is a persisting inflammatory disease it is important to establish the prognostic factors for the duration and severity of the disease. AIM: To evaluate serum concentrations of selected acute-phase proteins (APP) in patients with various forms of urticaria as compared to healthy volunteers and also to analyze these concentrations in different types of urticaria. Additionally, to evaluate the correlation between serum levels of selected APP and disease activity. MATERIAL AND METHODS: Serum concentrations of C-reactive protein (CRP), α1-acid glycoprotein (AGP), α1-antichymotrypsin (ACT), α1-antitrypsin (AT), ceruloplasmin (Cp), transferrin (Tf), α2-macroglobulin (α2M) and haptoglobin (Hp) were measured. Quantitative measurement was conducted using the rocket immunoelectrophoresis. Disease activity was assessed with the use of total symptom score. RESULTS: Analysis of serum APP concentrations revealed statistically higher serum concentrations of CRP, AGP and ACT in the entire group of patients with urticaria in comparison with the control group. In the entire group of patients with urticaria, CRP, AGP, ACT, Cp and Hp correlated positively with disease activity, intensity of pruritus and the number and size of urticarial wheals. Statistically lower serum concentrations of CRP, ACT, Cp and Hp were detected in the group of patients with acute urticaria (AU) and angioedema together, compared to the patients suffering from AU only. CONCLUSIONS: Patients with symptoms of various forms of urticaria present a distinct profile of serum APP concentrations. A significant correlation observed between CRP, AGP, ACT, Cp, Hp and clinical activity score points to the potential role of APP as markers of the urticarial activity.

Early acute phase response following total hip replacement.

BACKGROUND: The acute phase proteins are commonly known universal markers of the inflammatory process. The aim of the study was the evaluation of the acute phase response in the first 6 months THR. The secondary aim was to check if the type of hip replacement affects the acute phase response. MATERIAL AND METHODS: The study group consisted of 40 patients who underwent THA using uncemented (20) and cemented (20) endoprostheses. The concentrations of C-reactive protein, alpha-glycoprotein, and alpha-1-antichymotripsin, and microheterogeneity of AGP were evaluated. RESULTS: The blood levels of the acute phase proteins CRP, AGP, ACT rose significantly at 2 and 14 days after the surgery to return to preoperative values at 6 months after the surgery. The V3 variant of microheterogeneity of AGP, absent under normal conditions, and representative of acute inflammation, was found in a few patients preoperatively. In postoperative evaluations, it was found in the vast majority of the patients. CONCLUSIONS: The analysis of the profiles of the glycosylation of AGP shows that the presence of the acute inflammatory response immediately following total hip replacement, which later changes into persistent chronic inflammation, is more pronounced in patients receiving cemented endoprosthesis.

[The assessment of acute phase proteins as prognostic factors in patients surgically treated for non-small cell lung cancer]. / Ocena wybranych bialek ostrej fazy jako czynników rokowniczych u chorych leczonych chirurgicznie z powodu niedrobnokomórkowego raka pluca.

INTRODUCTION: The aim of the study was to assess quantitative changes of the acute phase protein (APP) serum level in patients with non-small cell lung cancer (NSCLC) who underwent a radical resection. We analysed the correlation between quantitative APP changes and: the survival rate, the histological type of the cancer, TNM stage and grading. MATERIAL AND METHODS: We analysed a group of 46 patients surgically treated for NSCLC from 2003 to 2004. The average age of patients was 61 (45 to 77 years). The most frequent histological types of cancer were: squamous cell lung cancer (24 patients) and adenocarcinoma (17 patients). The majority of them were in stage II B (15 patients) and III A (14 patients). We analysed serum levels of: C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), alpha1-antichymotrypsin (ACT), alpha1-antitrypsin (AT), alpha2-macroglobulin (M), ceruloplasmin (Cp), haptoglobin (Hp), and transferrin (Tf) by means of rocket immunoelectrophoresis by Laurell. RESULTS: The level of AT was significantly higher in patients with adenocarcinoma, as compared to other histological types of cancer. In the case of patients with squamous cell lung cancer, significantly higher M and Cp. We did not find any correlation between the APP level and grading. The levels of five APP: CRP, AGP, ACT, M and Cp were significantly higher in the group of patients with T3 or T4 category, while N1 or N2 status had significantly higher concentrations of AT, CRP and Hp. The multivariate analysis confirmed the influence of the following factors on long-term survival: N stage, histological type of cancer and preoperative serum levels of AGP and Hp. CONCLUSIONS: The serum concentration of some APP may correlate with the more aggressive clinical behavior of lung cancer. The patients with N1 or N2 stage of adenocarcinoma have significantly higher serum level of AT and the preoperative concentration of AGP and Hp correlates with the overall survival. These proteins could serve as prognostic factors in the risk assessment of the cancer recurrence after the surgical management.

[Acute phase response following total hip replacement and in patients with aseptic loosening]. / Odpowiedz ostrej fazy po endoprotezoplastyce stawu biodrowego i w aseptycznym obluzowaniu implantu.

INTRODUCTION: Aseptic loosening is a result of the chronic inflammatory reaction in periprosthetic tissues. Its intensity depends on the implants construction material and reactivity of the host's tissues. The aim of the study was the evaluation of the acute phase proteins in various periods following total hip replacement and comparison between acute phase response observed in patients with well-functioning implants and with aseptic loosening. MATERIAL: The study group consisted of 97 patients following THR due to the hip osteoarthritis. Patients of Group I were evaluated before the surgery and 6 months after primary THR. Group II consisted of patients 3-4 years after primary THR. Group consisted of patients with aseptic loosening. Patients of all groups were divided according to the implant type (cemente/uncemented). METHODS: Concentrations of evaluated acute phase proteins: C-reactive protein (CRP), transferrin (Tf) and alpha-glycoprotein were assessed using immunoelectrophoresis. RESULTS: In vast majority of patients (71-95%) following THR had present w3 variant of AGP which should be negative in physiological conditions. The average concentrations of AGP and AGP-RC were higher in patients following cemented THR. CONCLUSIONS: Implantation of the endoprosthesis raises a chronic inflammatory reaction expressed by changes in the profiles of acute phase proteins. This process is more visible in patients following cemented THR. The profiles of the acute phase proteins in patients with aseptic loosening were not different than those observed in patients with well-functioning implants, what makes them useless as a diagnostic tool for loosening. This lack of differences may be caused by adaptation of the generalised response to long lasting process of aseptic loosening

[The quantitative evaluation of the serum acute phase proteins (APP) of patients undergoing a curative resection for non-small cell lung cancer (NSCLC)]. / Ocena zmian ilosciowych bialek ostrej fazy w surowicy krwi chorych poddanych radykalnej resekcji niedrobnokomórkowego raka pluca.

The aim of this study was to quantitatively evaluate serum APP in patients undergoing the radical resection for NSCLC. The quantitative changes in APP were correlated with the cancer type, clinical staging and grading and the procedure type. Also, the impact of selected post-operative complications on the APP serum concentrations was evaluated. 46 patients undergoing surgery secondary to NSCLC in the years 2003-2004 were analyzed. The patients' age varied from 45 to 77 years with an average of 61.1. The most common pathological cancer type was the squamous cell cancer (24 patients) and adenocarcinoma (17 patients). The majority of the patients were stage IIB (15 patients) and IIIA (14 patients). The following APPs were evaluated in the patients' serum by Laurell rocket immunoelectrophoresis: C-reactive Protein (CRP), alfa-1 antichymotrypsine (alfa-1 ACT), alfa-1 antitrypsine (AT), alfa-2 macroglobuline (alfa2 M), ceruloplasmin (Cp), haptoglobine (Hp) and transferrin (Tf). Significantly higher serum AT level were found in patients with adenocarcinoma as compared to other pathology types. Patients with the squamous cell cancer had a significantly higher level of alfa-2 M and Cp. There was no significant difference in APP levels between the cancer grading types. In the group of patients with T3 or T4 stage the following five APPs were significantly elevated: CRP, AGP, alfa-1 ACT, alfa-2 M and Cp. Patients with regional lymph nodes metastasis (N2 or N2) had significantly higher level of AT, CRP and Hp. Patients undergoing more significant procedures (pneumonectomy, prolonged procedure time) and those with morbidities (rethoracotomy, blood transfusions) showed significantly higher levels of alfa-1 ACT, AGP and Cp. The most common post-operative complications were prolonged air-leak requiring probronchoscopy. In both complications a significantly higher level of AGP was observed. Patients with adenocarcinoma of the lung and regional lymph node metastasis have significantly higher serum levels of AT. This protein could be considered as one of the indicators of cancer involvement and could be a marker of the cancer recurrence. AGP is a protein that correlates positively with a more advanced clinical stage, and the extent of the surgical procedure as well as with the higher risk of morbidity. This could serve as a marker of higher post-operative complication rate.

Cytokines and heart rate variability in patients with chronic heart failure.

INTRODUCTION: Heart rate variability (HRV) analysis is a non-invasive method of assessment of the autonomic nervous system's effects on heart function. In chronic heart failure (CHF), decreased HRV correlates with the progression of the disease. It is also known that in CHF increased levels of proinflammatory cytokines are present. Because these molecules are believed to influence the nervous system at both the central and peripheral levels, their potential role in HRV reduction in the course of CHF has been proposed. AIM: The study was designed to verify potential relations between cytokines and HRV parameters in CHF patients. The concept of the study was driven by the recognition of controversies in this field and the paucity of published reports. METHODS: Forty-four patients with CHF and stable NYHA class I-IV symptoms and 15 healthy controls were enrolled in the study. Time-domain HRV analysis was performed based on of 24-hour Holter ECG monitoring. Plasma concentrations of soluble TNFalpha receptors sTNF-RI and sTNF-RII and interleukin 6 (IL-6) were measured using commercially available ELISA kits (Quantikine, RD Systems). RESULTS: In patients with CHF, HRV indices included in the analysis were significantly decreased, and the levels of cytokines increased in comparison with the control group. In the whole study population, both in the CHF patients and the control group, significant negative correlations were observed between sTNF-RI level and long-term HRV indices such as SDNN (r=-0.44; p=0.0006), SDANN (r=-0.44; p=0.0005) and short-time index SDNNI (r=-0.37; p=0.004). Similar negative correlations were found between sTNF-RII level and SDNN (r=-0.35; p=0.007), SDANN (r=-0.34; p=0.01), and SDNNI (r=-0.31; p=0.02), as well as between IL-6 level and SDNN (r=-0.41; p=0.001), SDANN (r=-0.44; p=0.0005) and SDNNI (r=-0.34; p=0.009). CONCLUSIONS: Significant negative correlations between TNF-alpha soluble receptors sTNF-RI, sTNF-RII and IL-6 levels and time-domain HRV parameters were observed in the study. Because the results of investigations conducted so far do not elucidate the cause-effect relationship, further studies are needed to clarify the mechanisms of HRV depression in CHF and the role of cytokines in this severe clinical condition.

[Cardiopulmonary exercise testing and cytokines in chronic heart failure. Comparison of patients with ischaemic and with dilated cardiomyopathy]. / Wyniki testu spiroergometrycznego i wartosci wybranych wskazników odczynu zapalnego u chorych z przewlekla niewydolnoscia serca. Porównanie chorych z kardiomiopatia niedokrwienna i rozstrzeniowa.

Heart failure (HF) is a complex clinical syndrome due to ischaemic heart disease, idiopathic cardiomyopathy, hypertension, valve heart disease and others. It is not clear if the etiology of HF influences decreased in this syndrome exercise tolerance. Controversial is also dependence of cytokine levels on etiology of HF. The aim of the study was to compare exercise capacity and cytokines levels in pts with ischaemic and dilated cardiomyopathy. We analyzed circulating levels of TNF-alpha and its soluble receptors sTNF-RI and sTNF-RII, and interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in 41 pts with CHF, functional class NYHA I-IV, mean EF--25.2 +/- 7.1%. For determination of cytokines level (using R & D System tests) venous blood was withdrawn after 30 minutes of supine rest. All underwent echocardiography and cardiopulmonary exercise stress testing. Dilated cardiomyopathy (DCM) was diagnosed in 21 pts, ischaemic (ICM) in 20 pts. Pts with DCM were younger then with ICM (48 +/- 6.6 vs 56 +/- 6.6 yrs; p = 0.001). There were no significant differences between groups concerning BMI and EF. There were no significant differences in the level of TNF-alpha and sTNF-RI between groups. There was a trend of increased sTNF-RII in pts with ICM (3179.7 +/- 832.7 vs 2699 +/- 680.1 pg/ml; p = 0,07), IL-1beta (2.55 +/- 2.41 vs 1.49 +/- 1.68 pg/ml; p = 0.087) and IL-6 (6.25 +/- 2.21 vs 4.98 +/- 3.64 pg/ml; p = 0.065), and significant increased ESR (11.2 +/- 9.5 vs 5.5 +/- 4.7 mm/h; p = 0.04). Peak VO2 was reduced in pts with ICM group as compared to those with DCM (14.1 +/- 3.7 vs 18.1 +/- 4.8 ml/kg/min; p = 0.0069). In chronic heart failure circulating levels of cytokines tended to be higher in pts with ischaemic origin of the syndrome. The exercise capacity is lower in ischaemic cardiomyopathy.

[Monitoring of IL-6 levels in patients after total hip joint replacement]. / Monitorowanie stezenia interleukiny 6 u chorych po implantacji endoprotez stawów.

Total hip replacement became a method of choice in treatment of the severe osteoarthritis. Despite the progress in constructing the implants and also the surgical technique, the number of complications rises together with the number of arthroplasties performed. The periprosthetic osteolysis and its consequence--the loosening is the one of the greatest problems of today's joint replacement. It creates the main obstacle for the long-term efficiency of the total hip arthroplasty. It was proved by the numerous research, wear debris of the implant induce the chronic periprosthetic inflammatory process. Many studies emphasize the influence of the proinflammatory cytokines on the bone metabolism. The aim of the study was the evaluation of the inflammatory process in patients with the severe osteoarthritis before the surgery and in subsequent periods after total hip replacements and also in patients with the aseptic loosening of the endoprosthesis, by the monitoring the levels of IL-6 in serum of the peripheral blood. The results suggest, that in patients following THA with the elevated level of IL-6, the inflammatory process was present. This inflammation may lead in future to the aseptic loosening of the implant.

Effect of subchronic ethanol treatment on plasma and cerebrospinal fluid leptin levels in rats selectively bred for high and low alcohol preference.

The effect of 5-week voluntary ethanol (EtOH) intake on plasma and cerebrospinal fluid (CSF) leptin levels was determined in adult male Warsaw high EtOH preferring (WHP) and low preferring (WLP) rats. EtOH treatment led to a decrease in leptin CSF concentration in WHP rats when compared to EtOH-naive WHP and control Wistar rats. On the contrary, in EtOH-treated WLP rats, both plasma and CSF leptin levels were increased in comparison with EtOH-naive animals. It can be concluded that EtOH treatment led to different response expressed especially by CSF leptin levels in WHP and WLP animals and it may be related to their genetic predisposition.