Clinical associations of C-reactive protein in systemic sclerosis

AIM: To evaluate incidence of C-reactive protein (CRP) rise and CRP associations with clinical manifestations in systemic sclerosis (SS). MATERIAL AND METHODS: CRP concentrations in blood serum were estimated with solid phase enzyme immunoassay in 21 SS patients (8 patients with diffuse SS--dSS and 13 patients with limited SS--lSS). Two patients with ISS had documented rheumatoid arthritis (RA)--SS/RA. Forty two healthy donors with normal levels of CRP served control. RESULTS: CRP was elevated in 10 (48%) of 21 SS patients. Mean CRP content was 9.87 +/- 7.73 mg/l (about 3 times higher than in the control group, p < 0.0001) in 20 eligible patients. A mean CRP level did not differ between ISS and dSS patients. RA patients had higher levels of CRP (p = 0.001). CRP was elevated in 4 of 5 (80%) patients with digital ulcers and only in 5 (27%) of 15 patients without ulcers, but the difference was insignificant as well as those in mean CRP in these subgroups. Content of von Willebrand factor antigen (Ag:vW) was high in 7 (33%) patients (mean 1.70 +/- 0.84 IU/ml) this being significantly higher than in the control group (p < 0.0001). CPR concentration closely correlated with that of Ag:vW (r = 0.52; p = 0.017). Close association was found between CRP level and ESR (r = 0.75; p < 0.001) and titer of antinuclear factor (r = 0.52; p = 0.035). CONCLUSION: A moderate rise of CRP level in about 50% cases of SS is associated with arthritis and cutaneous ulcers. A positive correlation between CRP content and Ag:vW in blood suggests that CPB concentrations may reflect severity of vascular damage in SS.     

Blood levels of angiogenin and vascular endothelial growth factor are elevated in myelodysplastic syndromes and in acute myeloid leukemia

Angiogenesis is of prognostic importance not only in solid tumors but also in malignant blood diseases. We measured levels of vascular endothelial growth factor (VEGF), angiogenin (ANG), and basic fibroblast growth factor (bFGF) in peripheral blood samples from 65 patients with myelodysplastic syndrome (MDS), from 25 patients with de novo acute myeloid leukemia (AML), and from 50 healthy donors. In matched samples, VEGF levels in serum were substantially higher than VEGF levels in plasma (380.7 +/- 56 pg/ml vs. 45.3 +/- 4.5 pg/ml, mean +/- SEM, p < 0.001), whereas serum and plasma levels of ANG were comparable and significantly correlated (r = 0.8; p < 0.01). Compared to normal controls (1.3 +/- 0.09 pg), serum levels of VEGF corrected for the peripheral blood platelet count (VEGF/10(6) platelets, VEGF(PLT)) were elevated in patients with refractory anemia (RA; 3.1 +/- 0.8 pg, p < 0.01), and reached maximal values in patients with advanced stage MDS (RAEB, RAEB-t) (3.5 +/- 0.6 pg, p < 0.001), de novo AML (3.6 +/- 1.1 pg, p < 0.05), and chronic myelomonocytic leukemia (CMML; 3.7 +/- 0.9 pg; p < 0.001). Levels of soluble ANG were elevated in RA (351 +/- 25.7 ng/ml, p < 0.001), in RAEB/RAEB-t (402 +/- 17.9 ng/ml; p < 0.001), in CMML (413.8 +/- 29.5 ng/ml; p < 0.001), and in patients with AML (305.1 +/- 17.1 ng/ml; p < 0.01, controls 255.4 +/- 8.1 ng/ml). Serum bFGF was neither elevated in MDS nor in AML patients. These results suggest that VEGF(PLT) is a marker of disease progression in MDS. Moreover, we show for the first time that elevated blood levels of ANG can be found in patients with myeloid malignancies, suggesting a role of ANG in the pathogenesis of these diseases.     

Cytokine expression in severe pneumonia: a bronchoalveolar lavage study.

OBJECTIVE: To assess the cytokine expression (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1beta, and IL-6) in severe pneumonia, both locally (in the lungs) and systemically (in blood). DESIGN: Prospective sequential study with bronchoalveolar lavage (BAL) and blood sampling. SETTING: Six-bed respiratory intensive care unit of a 1,000-bed teaching hospital. PATIENTS: Thirty mechanically ventilated patients (>48 hrs) were allocated to either the pneumonia group (n = 20) or a control group (n = 10). INTERVENTIONS: Protected specimen brush and BAL samples for quantitative cultures, and serum and BAL fluid TNF-alpha, IL-1beta, and IL-6 levels were measured on days 1, 3, and 7. In the control group, the procedure was done on day 1 only. MEASUREMENTS AND MAIN RESULTS: Serum TNF-alpha levels were significantly higher in patients with pneumonia compared with controls (35 +/- 4 vs. 17 +/- 3 pg/mL, respectively, p = .001). IL-6 levels in serum and BAL fluid were higher in pneumonia than in control patients (serum, 837 +/- 260 vs. 94 +/- 35 pg/mL, respectively, p = .017; BAL fluid, 1176 +/- 468 vs. 234 +/- 83 pg/mL, respectively, p = .05). On days 1, 3, and 7 in patients with pneumonia, IL-1beta levels turned out to be higher in BAL fluid than in serum (71 +/- 17 vs. 2 +/-1 pg/mL on day 1; 49 +/- 8 vs. 6 +/- 2 pg/mL on day 3; and 47 +/- 16 vs. 3 +/- 2 pg/mL on day 7 for BAL fluid and serum, respectively, p < .05). No significant correlation between BAL fluid cytokine levels and lung bacterial burden was shown in presence of antibiotic treatment. Although no clear relationship was found between BAL fluid and serum cytokines and mortality, there was a trend toward higher serum IL-6 levels in nonsurvivors (1209 +/- 433 pg/mL) with pneumonia compared with survivors (464 +/- 260 pg/mL). In addition, serum TNF-alpha and IL-6 correlated with multiple organ failure score (r2 = .36, p = .004 for both) and with lung injury score (r2 = .30, p = .01, and r2 = .22, p = .03, for TNF-alpha and IL-6, respectively). CONCLUSIONS: The present study describes the lung and systemic inflammatory response in severe pneumonia. The lung cytokine expression seems to be independent from the lung bacterial burden in the presence of antibiotic treatment. Because of the limited sample size, we did not find a clear relationship between serum and BAL fluid cytokine levels and outcome.     

Assessment of B-type natriuretic peptide in patients with pneumonia

The mammalian heart synthesises and secretes B-type natriuretic peptide (BNP), which has potent diuretic, natriuretic and vascular smooth muscle-relaxing effects as well as complex interactions with the hormonal and nervous systems. Recent studies described that BNP was acute phase reactant. In this study, we aimed to evaluate BNP levels in patients with pneumonia. Twenty-one patients with pneumonia and 21 healthy control subjects were enrolled in this study. Their serum levels of BNP were measured in addition to the standard evaluations. Leucocyte count [19.3 (13.2-25.7) 10(6)/ml vs. 9.55 (3.7-13.9) 10(6)/ml, p < 0.001], erythrocyte sedimentation rate [73 (57-81) mm/h vs. 35 (4-55) mm/h, p < 0.001], C-reactive protein (CRP) [127.72 (27-290) mg/l vs. 13.19 (3-41) mg/l, p < 0.001] and BNP [53.1 (17-91) pg/ml vs. 16.24 (1-38) pg/ml, p < 0.001] levels significantly decreased after treatment period. Initial BNP levels were significantly higher than control groups (53.10 +/- 15.07 pg/ml vs. 18.62 +/- 14.05 pg/ml, p < 0.001) and decreased after treatment to the levels comparable with control subjects. BNP levels correlated with CRP levels at admission (r = 0.716, p < 0.001). We have shown that BNP levels show a transient increase in patients with pneumonia and correlate well with CRP.     

Association between early detection of soluble TNF-receptors and mortality in burn patients

OBJECTIVES: To describe early sequential profiling of circulating levels of tumor necrosis factor alpha (TNF-alpha), TNF-1 and TNF-2 soluble receptors (sTNFR1 and sTNFR2), and of endothelin (ET-1) in patients with severe burn injury, and its association with mortality. DESIGN: Prospective study. SETTING: Intensive Care Burn Unit at a community hospital. PATIENTS: Twenty patients with total burn surface area (TBSA)> or = 30%. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients were enrolled within 6 h from the injury. Blood samples were drawn at zero, 6, 12, and 24 h for sequential ELISA measurement of plasma marker levels. Data are expressed as mean+/-SD. Age, TBSA, and inhalation injury were not significantly different between survivors ( n=9; 30+/-13 years, TBSA 40+/-12%) and nonsurvivors ( n=11, 38+/-15 years, TBSA 56+/-20%). sTNFR1 levels were increased in nonsurvivors (2937+/-1676 pg/ml; 4548+/-1436 pg/ml) as compared to survivors (1313+/-561 pg/ml; 2561+/-804 pg/ml) at 6 h and 24 h, respectively ( P=0.01 and 0.002). sTNFR2 levels were significantly increased in nonsurvivors (4617+/-1,876 pg/ml vs 2611+/-1,326 pg/ml) only at 6 h ( P=0.015). TNF-alpha and ET-1 levels were not different between nonsurvivors and survivors. After adjustment for TBSA, sTNFR1 and sTNFR2 remained significantly higher in nonsurvivors. CONCLUSION: Early and progressive increase in sTNFR1 and sTNFR2 levels is associated with higher risk for poor outcome in severely burned patients.     

Antibodies to cyclic citrullinized peptide in rheumatoid arthritis

AIM: To estimate a diagnostic value of antibodies to cyclic citrullinized peptide (CCP) in rheumatoid arthritis (RA). MATERIAL AND METHODS: The study was made of 85 RA patients. Of them, 48 patients had early RA, i.e. of 8 month and less duration. The control group consisted of 35 patients with non-differentiated arthritis (NDA) and 8 healthy donors. Concentrations of CCP antibodies, rheumatoid factor (RF) IgM and RF IgA were measured with enzyme immunoassay (EIA). RESULTS: The level of CCP antibodies in RA patients (76.3 +/- 43.8; median 100.0 U/ml) was significantly higher than in NDA patients (25.1 +/- 43.9; median 0.8 U/ml; p < 0.05) or in donors (0.38 +/- 0.36; median 0.2 U/ml; p < 0.05). A correlation was found between the CCP antibodies level and that of RF IgM (chi2 = 15.4; p = 0.001) and RF IgA (chi2 = 10.3; p = 0.001). Sensitivity (82%) and specificity (90%) of CCP antibodies in RA diagnosis was higher than these parameters for RF IgM and IgA (78%, 86% and 72%, 83%, respectively). Simultaneous tests for CCP antibodies, RF IgM and RF IgA led to a 93% specificity. CCP antibodies were detected in 50% patients seronegative by RF IgM and in 62% patients seronegative by IgA. Detection of CCP antibodies was closely associated with early RA (chi2 = 30.8; p = 0.0001). CONCLUSION: The EIA for CCP antibodies is a sensitive and specific serological test for early RA diagnosis.     

Serum protein oxidation in patients with rheumatoid arthritis and effects of infliximab therapy

OBJECTIVE: To examine protein oxidation in rheumatoid arthritis (RA) and evaluate its evolution after infliximab therapy in a subgroup of patients. METHODS: Seventy-one consecutive patients with RA were included. Among them, 30 patients refractory to conventional therapy were treated with infliximab. Serum markers of oxidative stress were determined at baseline and before the infusions of infliximab at weeks 6 and 30. Baseline values were compared with those in 30 healthy volunteers. RESULTS: Mean levels of serum carbonyl groups were significantly higher in RA patients than in controls (1.29+/-0.76 versus 0.58+/-0.39 nmol/mg of protein, p<0.0001), whereas thiol levels were found to be lower (238.3+/-61.6 versus 316.5+/-54.8 micromol/L, p<0.0001). Thiol levels inversely correlated with the disease activity score (r=-0.42, p=0.004), and with CRP values (r=-0.45, p=0.001). Immunoblots showed that albumin and heavy chain immunoglobulin were oxidized more markedly than in healthy volunteers. Significantly lower levels of thiol groups were detected in patients with refractory RA disease (208.9+/-66.8 versus 264.2+/-43.0 micromol/L, p<0.0004) but concentrations of carbonyl groups were similar. Short-term treatment with infliximab significantly decreased carbonyl groups (0.97+/-0.47 nmol/mg protein, p=0.02) and increased thiol (231.2+/-48.7 micromol/L, p=0.02) levels. CONCLUSION: Our results highlight free radical protein damage in RA and a link with inflammation, as underlined by the beneficial effects of infliximab.     

Serum leptin levels in rheumatoid arthritis and relationship with disease activity

OBJECTIVES: This study was performed to evaluate serum leptin levels in rheumatoid arthritis (RA) patients and investigate the correlation with serum tumor necrosis factor alpha (TNF-alpha) levels and clinical and laboratory parameters of disease activity. METHODS: Fifty patients with RA and 34 control subjects were included. Disease activity score 28 (DAS28) was calculated for each patient. Laboratory activity was assessed by examining erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Immunoradiometric assay was used for measuring serum leptin levels (ng/mL). Serum TNF-alpha levels (pg/mL) were measured by sandwich enzyme-linked immunosorbent assay method in 41 of 50 RA patients and in 24 control subjects. RESULTS: Age, sex and body mass index (BMI) did not show a statistically significant difference between RA and control subjects (P > 0.05). Serum leptin levels were higher in RA (P = 0.000). In RA patients, there were no correlations between serum leptin levels and disease duration, swollen and tender joint counts, DAS28, CRP, ESR, serum TNF-alpha levels, oral glucocorticoid and methotrexate usage (P > 0.05). There was no statistically significant serum leptin level difference between patients with high disease activity and mild and low disease activity (P = 0.892). Serum leptin levels positively correlated with BMI in both patient and control groups (P < 0.05). In both groups, mean serum leptin levels were higher in women than men. CONCLUSIONS: Even though serum leptin levels were found to be significantly higher in RA patients than in control subjects in this study, there was no correlation between serum leptin levels and TNF-alpha levels, clinical and laboratory parameters of disease activity. However serum leptin levels positively correlated with BMI in both patient and control groups. In RA, circulating leptin levels do not seem to reflect disease activity.     

Plasma concentrations of atrial natriuretic peptide in various diseases

Using a radioimmunoassay for atrial natriuretic peptide (ANP) we studied plasma concentrations of immunoreactive ANP in order to investigate the pathophysiological role of ANP in patients with various diseases. Plasma ANP levels were elevated in patients with congestive heart failure (394 +/- 260 pg/ml, n = 8) and chronic renal failure (219 +/- 86 pg/ml, n = 11). In patients undergoing hemodialysis plasma ANP levels were markedly high and decreased after hemodialysis from 433 +/- 166 pg/ml to 204 +/- 92 pg/ml (n = 11). ANP was removed from blood to dialysate (21 +/- 13 pg/ml of dialysate, n = 6, dialysate flow: 500 ml/min). Plasma ANP level was conversely correlated with creatinine clearance (r = -0.812, p less than 0.001) in patients with renal diseases (n = 29). In patients with atrial fibrillation, pace maker implantation, lung disease, chronic glomerulonephritis, nephrotic syndrome, essential hypertension, liver disease and cerebrovascular disease, plasma ANP levels were not significantly different from those in normal subjects (70 +/- 32 pg/ml, n = 28). These results suggest that ANP may be a circulating hormone playing pathophysiological roles in congestive heart failure and chronic renal failure.     

TNF-alpha and its receptors mediate graft rejection and loss after liver transplantation.

Tumour necrosis factor-alpha (TNF-alpha) plays a pivotal role in the immune response and mediates inflammation by its receptors (TNF-RI and TNF-RII), as observed during rejection episodes and impaired graft function after liver transplantation. TNF-alpha and its receptors were analysed by an ELISA technique in serum samples from 77 consecutive liver transplantations in 63 patients. Samples were collected preoperatively from donors and recipients and then daily in the first two postoperative weeks. Peak levels of TNF-alpha and its soluble receptors (sTNF-RI and sTNF-RII) in the first and second postoperative week correlated with the extent of reperfusion injury. Impaired graft functions correlated with high sTNF-RI levels preoperatively (> 5 ng/ml, p = 0.01) and in the postoperative period (> 16 ng/ml, p = 0.02). Significantly increased TNF-alpha (> 25 pg/ml, p = 0.009) and sTNF-RI levels (> 5 ng/ml, p = 0.05) were found in donors of grafts with a high rejection risk. Elevated levels of TNF-alpha in the postoperative period correlated with an increased rejection risk (> 90 pg/ml, p = 0.02). The activity of the immune system with high concentrations of TNF-alpha and its receptors both in the recipient and the transplant donor seems to play an essential role in allograft development.     

Tumour necrosis factor-alpha levels in hepatitis B virus-related chronic active hepatitis and liver cirrhosis and its relationship to Knodell and Child-Pugh scores

Although both chronic active hepatitis-B (CAH-B) and liver cirrhosis (LC) are characterised by various degrees of inflammation and hepatocyte necrosis, in advanced stage cirrhosis, marked fibrosis develops and inflammation and tissue necrosis diminishes. In this study, we aimed to investigate serum tumour necrosis factor-alpha (TNF-alpha) concentration in patients with CAH-B and LC and its relationship to disease activity. Serum samples were taken from 30 patients with CAH-B and 30 with LC at different stages of the disease. TNF-alpha concentrations were measured by the ELISA technique. Results were compared with those of 30 healthy controls. Mean plasma TNF-alpha levels were found as 2.47 +/- 2.98, 0.8 +/- 1.21 and 0.72 +/- 1.08 pg/ml in CAH-B, LC and control groups, respectively. TNF-alpha levels were significantly higher in CAH-B group than LC and control groups (p <0.01 and p < 0.05, respectively). Although mean plasma TNF-alpha level of cirrhotic patients at Child-A stage was markedly high (3.31 +/- 0.15), no significant difference has been found between LC and control groups (p > 0.05). TNF-alpha concentrations were positively correlated with hepatitis activity index (Knodell's score) in CAH-B group whereas negatively correlated with Child-Pugh score in LC group (r =0.73, p < 0.01 and r = -0.42, p < 0.05, respectively). Our study showed that TNF-alpha level increases in patients with CAH-B correlated with histologic activity index. So it can be used to evaluate disease activity. Additionally, marked reduction of TNF-alpha concentration in advanced cirrhosis suggested that TNF-alpha production is determined by hepatic damage and inflammation.     

类风湿关节炎患者血清白细胞介素-21水平检测及临床意义

目的检测类风湿关节炎(RA)患者血清中白细胞介素-21(IL-21)的水平,分析其临床意义。方法收集RA患者76例,采用双抗体夹心酶联免疫吸附试验(ELISA)检测RA患者及37例正常对照者血清IL-21水平,并分析血清IL-21水平与RA各临床及实验室指标的相关性。计量资料的比较采用Mann-Whitney U检验或单因素方差分析,相关性分析采用Spearman相关分析。结果 RA患者血清IL-21水平为86.5(64.1～130.1)pg/ml,明显高于正常对照组[65.0(40.0～90.3)pg/ml],差异有统计学意义(U=957.5,P=0.006);类风湿因子(RF)三个亚型IgM、IgA、IgG及抗环瓜氨酸肽(CCP)抗体阳性组RA患者血清IL-21水平与其自身抗体均呈正相关(r分别为0.300、0.382、0.370、0.372;P均<0.05)。RA患者RF(IgM、IgA)、CCP抗体阳性组血清IL-21水平显著高于阴性组[82.2(57.0～126.1)pg/ml]和76.9(52.0～201.4)pg/ml,U=176.5,P=0.024;95.4(62.1～144.6)pg/ml和70.6(43.0～110.8)pg/ml,U=282.5,P=0.016;82.9(51.0～145.1)pg/ml和76.5(63.4～144.6)pg/ml,U=333.0,P=0.031],差异有统计学意义。患者血清IL-21水平与触痛关节数(TEN28)及肿胀关节数(SW28)均呈正相关(r分别为0.342、0.200;P均<0.05),但IL-21与DAS28评分、C-反应蛋白、血沉、年龄、病程等均无明显相关性。结论 IL-21在RA患者血清中高表达,并与RF、抗CCP抗体密切相关,提示IL-21可能是RA发病机制的环节之一。     

Effects of repeated infliximab therapy on serum lipid profile in patients with refractory rheumatoid arthritis

BACKGROUND: Patients with rheumatoid arthritis (RA) frequently display an atherogenic lipid profile which has been linked with inflammation. Tumor necrosis factor-alpha (TNF-alpha), a pivotal pro-inflammatory cytokine in RA may be involved in the development of the disturbed lipid metabolism. We investigated whether infliximab, an anti-TNF-alpha therapy, may modify the lipid profile. METHODS: 56 consecutive RA patients were treated with infliximab (3 mg/kg at weeks 0, 2, 6, 14, 22, 30). Lipid profile and CRP were assayed at baseline and before infusion at weeks 6 and 30. Baseline values were compared with those in 56 healthy volunteers. RESULTS: At baseline, the concentrations of HDL-cholesterol were lower in RA patients than in the controls (1.3+/-0.4 vs. 1.5+/-0.2 mmol/L; p<0.01). The triglyceride concentrations (1.6+/-0.8 vs. 1.3+/-0.4 mmol/L, p<0.01), the ratio of total cholesterol/HDL-cholesterol (4.3+/-1.6 vs. 3.2+/-0.5, p<0.001) and LDL-cholesterol/HDL-cholesterol (2.6+/-1.2 vs. 1.7+/-0.5, p<0.001) were significantly higher in RA patients than in controls. After 6 weeks of infliximab therapy, the mean total cholesterol concentration increased by 25% (p<0.001), LDL-cholesterol by 24% (p<0.001) and HDL-cholesterol by 30% (p<0.001). The decrease in CRP levels to 30 week inversely correlated with the increase in HDL-cholesterol (r=-0.47, p=0.005). CONCLUSIONS: Infliximab administration is associated with important increases in cholesterol levels in all its forms but as no significant beneficial effect on the atherogenic ratio.     

The activity of nonspecific inflammation in hypertensive patients

AIM: To study the indices of nonspecific inflammation (C-reactive protein--CRP, interleukine 6--IL-6) in patients with essential hypertension (EH) as compared to a circadian profile of blood pressure (BP); changes of CRP in the course of therapy with indapamide-retard and ACE inhibitor perindopril. MATERIAL AND METHODS: The trial enrolled 81 patients with hypertension of stage I-II, moderate and high risk, aged 45.1 +/- 1.3 years, free of chronic inflammatory disease exacerbation, 2 months and more after acute respiratory diseases and 2-week absence of antihypertensive therapy. CRP was estimated by turbidimetry, IL-6--by ELISA, circadian BP monitoring was made using TM 2421 device. Seventeen patients were randomized to receive ariphon retard (Servier), twenty patients--prestarium. The data were processed with STATISTICA 6 programs. RESULTS: CRP level in the patients was 7.0 +/- 1.6 mg/l; an elevated CRP concentration (> 3 mg/l) was registered in 55% patients. These patients demonstrated a positive correlation of CRP concentration with the data of 24-h systolic BP (r = 0.37, p < 0.05) and 24-h diastolic BP (r = 0.43, p = 0.003) monitoring, abnormal circadian rhythm of BP (nondippers). IL-6 in the examinees was 6.7 +/- 1.3 pg/ml. An elevated IL-6 concentration was detected in 30%. In such patients a positive correlation was found between IL-6 and 24-h systolic and diastolic BP (r = 0.88; p < 0.05 and r = 0.97; p < 0.01, respectively). CONCLUSION: A positive correlation between CRP, IL-6 and BP may evidence for involvement of nonspecific inflammation in the course of EH. Patients with elevated CRP responded to ariphon retard with positive CRP dynamics. This can be explained by a relief of chronic hemodynamic stress. A positive CRP dynamics in response to prestarium can be mediated by block of angiotensin II.     

Can the inflammation markers of patients with high peritoneal permeability on continuous ambulatory peritoneal dialysis be reduced on nocturnal intermittent peritoneal dialysis?

BACKGROUND: Patients with high peritoneal permeability have the greatest degree of inflammation on continuous ambulatory peritoneal dialysis (CAPD), which may be associated with their higher mortality. Nocturnal intermittent peritoneal dialysis (NIPD; "dry day") may decrease inflammation by reducing the contact between dialysate and peritoneum and/or providing better fluid overload control. Therefore, the aims of this study were to determine and compare serum and dialysate concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) of patients with high or high-average peritoneal transport on CAPD, changed to NIPD, and ultimately to continuous cyclic peritoneal dialysis (CCPD). METHODS: Crossover clinical trial in 11 randomly selected patients. All subjects had been on CAPD and were changed to NIPD, and ultimately to CCPD (6.4 +/- 3.1 months after initiation of study). All patients used glucose-based dialysate. Evaluations of clinical and biochemical parameters, dialysis adequacy, and serum and dialysis inflammation markers were performed at baseline on CAPD, 7 - 14 days after changing to NIPD, 7 - 14 days after switching to CCPD, and after 1 year of follow-up. All patients used only 1.5% glucose dialysate during evaluation days. CRP was determined by nephelometry, and IL-6 and TNF-alpha by ELISA. RESULTS: Seven patients were high transporters and 4 high average. Ultrafiltration increased (p < 0.05) when patients changed from CAPD [0.38 L (-0.3 - 1.1 L)] to NIPD [2.64 L (0.7 - 4.7 L)]; it then decreased on CCPD [0.88 L (0.4 - 1.3 L) and at the end of study [0.65 L (0.3 - 1.0 L)]. This better fluid overload control was accompanied by decreased weight and systolic and diastolic blood pressure when patients changed from CAPD (89 +/- 13 kg, 160 +/- 23 and 97 +/-9 mmHg, respectively) to NIPD (86 +/- 17 kg, 145 +/- 14 and 86 +/- 9 mmHg, respectively), and increased weight and systolic and diastolic blood pressure on CCPD (85 +/- 15 kg, 143 +/-23 and 88 +/- 14 mmHg, respectively) and at the end of follow-up (87 +/- 16 kg, 155 +/- 24 and 89 +/- 12 mmHg, respectively). Median serum CRP decreased (p = 0.03), from 3.8 (1.6 - 8.5) mg/L on CAPD to 1.0 (0.4 - 4.4) mg/L on NIPD, but increased on CCPD [1.8 (1.3 - 21) mg/L] and at the end of the study [3.2 (0.3 - 8.2) mg/L]. Dialysate CRP decreased nonsignificantly, from 0.10 (0 - 0.5) mg/L on CAPD to 0 (0 - 0.03) mg/L on NIPD, to 0.01 (0 - 0.08) mg/L on CCPD, and to 0 (0 - 0) mg/L at final evaluation. Serum TNF-alpha concentration decreased, from 0.14 (0.04 - 0.6) pg/mL on CAPD to 0.01 (0 - 0.08) pg/mL on NIPD, and then increased to 0.06 (0 - 0.4) pg/mL on CCPD and to 0.11 (0 - 0.2) pg/mL at the end of the study; whereas dialysate TNF-alpha decreased, from 0.08 (0.03 - 0.2) pg/mL on CAPD to 0.04 (0 - 0.2) pg/mL on NIPD, and to 0 (0 - 0) pg/mL and 0 (0 - 0.05) pg/mL on CCPD and final evaluation respectively. Serum IL-6 decreased (p = 0.07), from 2.5 (2.0 - 4.2) pg/mL on CAPD to 1.0 (0.7 - 2.0) pg/mL on NIPD, and to 1.0 (0.8 - 2.9) pg/mL on CCPD and 1.0 (0.5 - 9.8) pg/mL at the end of the study; whereas dialysate levels remained similar on CAPD [8.0 (3.7 - 13) pg/mL] and NIPD [7.8 (5.1 - 23) pg/mL], and increased on CCPD [11.2 (9.5 - 19) pg/mL] and at final evaluation [11.2 (8.3 - 15) pg/mL]. CONCLUSIONS: NIPD significantly decreased serum CRP and displayed a trend to decrease TNF-alpha and IL-6 serum concentrations compared with CAPD; whereas CCPD tended to reverse these effects. These results did not appear to be due to decreased local peritoneal inflammation, but they could be associated with better control of fluid overload on NIPD. Thus, NIPD, as Long as the residual renal function allows it, may be useful in reducing the systemic inflammation of patients with high peritoneal membrane permeability.     

血浆miR-223-3p，PCT，IL-6和CRP水平联合检测对脓毒症实验诊断及预后的价值研究

目的　探讨微小核糖核酸-223-3p（miR223-3p）联合降钙素原（PCT）、白细胞介素-6（IL-6）及C反应蛋白（CRP）对脓毒症诊断及预后预测的意义。方法　选取2018年1月～2020年10月三亚市中医院和三亚中心医院收治的脓毒症患者146例,根据患者28天的生存情况,将其分为存活组（n=101）和死亡组（n=45）。选取同期60例体检健康者作为对照组。检测各组血浆miR-223-3p,PCT,IL-6及CRP水平。应用受试者工作特征（ROC）曲线分析miR-223-3p联合PCT,IL-6及CRP对脓毒症诊断及预后预测的价值。结果　脓毒症组血浆miR-223-3p（2.15±0.92 vs 0.37±0.08）,PCT（13.50±6.48 ng/ml vs 0.02±0.01ng/ml）,IL-6（74.12±15.70 pg/ml vs 5.37±1.45pg/ml）及CRP（37.26±10.15 mg/L vs 3.82±1.46mg/L）水平均明显高于对照组,差异均有统计学意义（t=8.783~14.620,P<0.001）。死亡组血浆miR-223-3p（3.04±1.16 vs 1.31±0.50）,PCT（21.28±10.28 ng/ml vs 6.72±3.15ng/ml）,IL-6（102.83±21.75 pg/ml vs 56.17±10.20pg/ml）及CRP（56.40±15.30mg/L vs 25.75±8.24mg/L）水平均明显高于存活组,差异均有统计学意义（t=7.415~16.317,均P<0.001）。ROC曲线分析显示,miR-223-3p联合PCT,IL-6及CRP诊断脓毒症的曲线下面积最大（0.905,95%CI :0.847~0.968）,其敏感度和特异度分别为92.0%和83.4%;miR-223-3p联合PCT,IL-6及CRP预测脓毒症患者死亡的曲线下面积最大（0.933,95%CI :0.875～0.990）,其敏感度和特异度为分别95.3%和87.5%。相关性分析显示,脓毒症患者血浆miR-223-3p表达水平与PCT,IL-6及CRP均呈正相关性（r=0.825,0.792,0.753,均P<0.001）。结论　脓毒症患者血浆miR-223-3p表达水平明显升高,联合PCT,IL-6及CRP检测对脓毒症的诊断及预后预测具有良好的价值。     

A cytokine status in chronic alcoholic and biliary pancreatitis

AIM: To determine characteristics of a cytokine status in chronic pancreatitis (CP) depending on etiological factor, stage of the disease, complications, therapy. Material and methods. 72 patients had chronic alcoholic pancreatitis (CAP), 38 patients--chronic biliary pancreatitis (CBP). Control group consisted of 20 healthy subjects. RESULTS: At early stages and height of CAP exacerbation, concentrations of IL-1beta, IL-6, IL-8, TNF-gamma and TNFalpha were elevated (951.1 +/- 104.2 pg/ml; 172.8 +/- 24.3 pg/ml; 432.6 +/- 68.5 pg/ml; 823.3 +/- 97.5 pg/ml; 158.7 +/- 19.6 pg/ml, respectively). Regenerative processes in CP were accompanied with IL-4 elevation to 614.9 +/- 64.6 pg/ml. In CAP without complications and with them the levels of cytokines differed significantly. The level of TGF-beta1 stimulating development of fibrosis was in CAP patients 627.8 +/- 92.2 pg/ml, in CAP patients with complications--796.8 +/- 102.5, in the controls--40.2 +/- 4.6 pg/ml (p < 0.05). In early stages of CBP exacerbation, IL-1beta rose to 527.2 +/- 62.7 pg/ml, IL-6--to 80.9 +/- 11.4 pg/ml, IL-8--to 290.4 +/- 46.8 pg/ml, INF-gamma to 853.3 +/- 91.6 pg/ml; TNF-alpha--to 79.7 +/- 8.3 pg/ml, TGF-beta1--534.1 +/- 78.4 pg/ml. With attenuation of acute syndromes and development ofregeneration, levels of IL-4 went up (226.7 +/- 32.4 pg/ml). CONCLUSION: CP is accompanied by increase in cytokine contents depending on the etiological factor, variants of course, stage, presence of complications.     

Discordant regulation of CRP and NT-proBNP plasma levels after electrical cardioversion of persistent atrial fibrillation

BACKGROUND: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) have been suggested to be prognostically relevant markers in patients with cardiovascular disease. Additionally, BNP and CRP plasma levels seem to be independently elevated in patients with atrial fibrillation (AF). However, there are only sparse data about the significance and temporal course of these plasma markers after restoration of sinus rhythm (SR). METHODS: We performed a prospective study in consecutive patients with symptomatic atrial fibrillation. NT-proBNP and CRP plasma levels were measured before and one month after electrical cardioversion (CV). Patients with infections, an acute coronary syndrome, or surgery 4 weeks prior to CV, were excluded. RESULT: Twenty-five patients (men 84%, age 66 +/- 8 years, duration of AF 90 +/- 75 days, left ventricular ejection fraction 0.57 +/- 0.11) were analyzed. At follow-up (33 +/- 6 days after CV) 14 patients (56%) were in SR and 11 patients (44%) in AF. In patients with SR there was a significant reduction of NT-proBNP levels (baseline 1647 +/- 1272 pg/mL, follow-up 772 +/- 866 pg/mL, P < 0.05), even in a subgroup of patients (n = 10) with normal left ventricular ejection fraction (1262 +/- 538 vs 413 +/- 344 pg/mL, P < 0.001). CRP levels in patients with SR were similar at baseline and at follow-up (3.5 +/- 3.6 vs 3.2 +/- 2.5 mg/L, P = 0.8). CONCLUSION: We conclude that even in patients with normal left ventricular ejection fraction restoration of sinus rhythm leads to a significant reduction of NT-proBNP plasma levels. In contrast, CRP plasma levels seem not to be influenced during the first 4 weeks after electrical cardioversion.     

Levels of anti-inflammatory cytokines interleukin-2, interleukin-8, and soluble interleukin-2 receptor in blood of patients with various forms of ischemic heart disease

AIM: To quantify interleukin-8 (IL-8), interleukin-2 (IL-2) and soluble receptor of IL-2 (sIL-2r) in blood serum of patients with various forms of ischemic heart disease (IHD). MATERIAL AND METHODS: Levels of IL-8, IL-2 and sIL-2r were measured with enzyme immunoassay (EIA) in the serum of 75 patients with IHD: angina of effort (group 1), progressive angina (group 2) and acute myocardial infarction (group 3). The EIAs were performed at admission and 2 weeks later. RESULTS: Baseline levels of IL-2 in group 1 and 2 patients were close (9.1 +/- 1.6 and 10.1 +/- 3.8 pg/ml) being significantly lower in group 3 (0.81 +/- 0.57 pg/ml, p < 0.01). 14 days of therapy did not change the values noticeably. IL-8 level was the highest in group 1 (94.2 +/- 27.6, 20.03 +/- 7.4, 22.47 +/- 4.8 pg/ml, respectively). sIL-2r in the three groups did not vary greatly (73.95 +/- 12.23, 89.46 +/- 18.17, 89.2 +/- 14.17 pg/ml, respectively). SIL-2r levels rose in 2 weeks in group 3 (to 147.67 +/- 18.17 pg/ml). CONCLUSION: It is confirmed that IL-2, IL-8 and sIL-2r take part in pathogenesis of IHD. IL-2 and IL-8 levels are persistently high in anginal patients while in patients with acute myocardial infarction they are low. Low concentrations of IL-2 in the latter may be attributed to high levels of its soluble receptor.