Rosuvastatin Lowers Systemic Inflammatory Response in Coronary Artery Bypass Graft Accompanied by Cardiopulmonary Bypass Surgery: A Randomized Controlled Study.

PURPOSE: Cardiopulmonary bypass (CPB) is commonly associated with a systemic inflammatory response that may lead to severe complications. Classic signs of systemic inflammatory response syndrome are complement activation and changes in cytokine and acute phase reactant levels. The effects of rosuvastatin after CPB on interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-18 (IL-18) and High Sensitivity C-Reactive Protein (hs-CRP) levels were investigated. METHODS: Thirty-seven male and thirteen female patients (total=50) aged 42 to 78 years, who had coronary bypass surgery due to coronary artery disease were randomly divided into two groups. The 25 patients in the control group were administered placebos. The 25 in the treatment group were administered 20 mg rosuvastatin tablets daily between preoperative day 7 and postoperative day 28. Blood samples were taken at six time points; before induction of anesthesia (T1), during CPB (T2), five minutes after removal of cross clamp (T3), after protamine infusion (T4), postoperative day three (T5) and postoperative day 28 (T6). Data points were expressed as mean ± standard deviation (SD). RESULTS: Rosuvastatin lowered IL-6 levels at T4, T5 and T6 time points (T4, T5, T6 p < 0.05), and elevated IL-10 levels at T3 and T4 (T3, T4 p < 0.05). IL-18 levels were also elevated at multiple time points. Rosuvastatin also lowered hs-CRP levels and cholesterol levels at T6 (p < 0.05). CONCLUSION: Administering 20 mg/day of rosuvastatin between preoperative day 7 and postoperative day 28 may result in fewer complications in certain (especially intraoperative) cases of systemic inflammatory response caused by the CPB technique used in coronary bypass surgery.

Serum adiponectin, anemia and left ventricular dimensions in patients with cardiac cachexia.

OBJECTIVES: Our study aims to determine the role of serum adiponectin in chronic heart failure (CHF) and cardiac cachexia (CC). METHODS: Ninety consecutive patients were included in the study. Patients were divided into three groups: 30 CHF patients with CC, 30 CHF patients without CC, and 30 healthy individuals. Adiponectin levels were measured through human ELISA kits. RESULTS: Levels of serum adiponectin were significantly higher in the CHF patients with cachexia in comparison with the other groups (CHF with CC: 58.4 ± 15.5 ng/ml vs. CHF without CC: 24 ± 6.7 ng/ml and controls: 7.7 ± 3.4 ng/ml; p = 0.001). Serum adiponectin was negatively correlated with BMI, high-sensitivity C-reactive protein, and hemoglobin (r = -0.37, p = 0.02; r = -0.29, p = 0.02; r = -0.18, p = 0.03, respectively) in the CHF patients with cachexia. Additionally, serum adiponectin levels were positively correlated with B-type natriuretic protein levels, left ventricle end-diastolic and end-systolic diameters (r = 0.36, p = 0.02; r = 0.46, p = 0.01; r = 0.49, p = 0.006, respectively) in the CHF patients with cachexia. CONCLUSION: Our findings suggest that adiponectin may play a critical role in the pathogenesis of cardiac remodeling and anemia in CC.

Adiponectin levels in coronary artery ectasia.

Etiopathogenesis of coronary artery ectasia (CAE), which is defined as abnormal dilatation of a segment of the coronary artery to 1.5 times of an adjacent normal coronary artery segment, is unclear. However, it is speculated that CAE develops in the atherosclerosis process through degeneration of coronary artery media layer. Our objective in this study is to compare levels of adiponectin between cases with CAE and normal coronary anatomy, and to examine whether adiponectin plays a role in CAE etiopathogenesis. The study registered a total of 66 cases, consisting of CAE cases (group 1, n = 36) and cases with normal coronary anatomy (group 2, n = 30). Taking coronary artery diameters of the control group cases as the reference, patients with abnormal segments 1.5 times larger than the adjacent segments were accepted as CAE. Serum adiponectin levels were 4.31 +/- 2.02 microg/ml in group 1 and 6.73 +/- 4.0 microg/ml in group 2 (P = 0.02). High-sensitivity C-reactive protein was 4.8 +/- 3.8 mg/l in group 1 and 3.6 +/- 3.4 mg/l in group 2 (P > 0.05). There was a negative correlation between ectatic coronary artery diameter and plasma adiponectin level (P = 0.03; r = -0.339). It was known that adiponectin levels dropped in atherosclerotic heart disease. In this study we found low plasma adiponectin levels in acquired CAE, attributed to atherosclerosis. Therefore, we think that adiponectin might be playing a role in etiopathogenesis and progression of CAE. This in turn may indicate that hypo-adiponectinemia may be useful in revealing a realized risk in CAE. However, larger, randomized, multicenter studies are required to examine the role of adiponectin in the development of CAE.

Anti-HDV seroprevalance among patients with previous HBV infection.

OBJECTIVE: This prospective study aimed to determine the prevalence of anti-HDV seropositivity among subjects who had previous hepatitis B virus (HBV) infection. METHODS: Subjects who were admitted to the gastroenterology inpatient clinic of our hospital between August 2016 and July 2017 were screened for previous HBV infection. The subjects who had HBV serology compatible with resolved HBV infection were recruited in the study, and the seroprevalance of anti-HDV was studied. Participants answered a short questionnaire regarding their family history of chronic hepatitis B (CHB) and chronic hepatitis D (CHD) infection and risk factors for transmission. Subjects who were anti-HDV positive were recalled for a control visit, and HBV-DNA and HDV-RNA were assayed in the blood samples of the responders. RESULTS: Among 554 subjects who had previous HBV infection, 53 (9.6%) were anti-HDV positive. The mean age was 63.1±15.4 years in the anti-HDV-positive group and 65.9±15.6 years in the anti-HDV-negative group (p=0.19). The most common risk factor for both groups was dental procedures (89% vs 80%, p=0.33). Anti-Hbc IgG, anti-Hbs, and anti-HBeAg seropositivity did not differ between the anti-HDV-positive and -negative groups (for all, p>0.05). Although HDV-RNA was not detectable in all studied samples, only one subject had detectable HBV-DNA in the anti-HDV-positive group. CONCLUSION: This study highlighted the prevalence of anti-HDV among subjects who had resolved HBV infection. Long-term follow-up studies, including after the resolution of both infections, are needed to explore HBV-HDV interactions and the behavioral patterns of these viruses.

Atopic dermatitis and Valpha24+ natural killer T cells.

OBJECTIVE: Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers and is often the first step in the atopic march that results in asthma and allergic rhinitis. Helper T cells and their cytokines, in addition to IgE and eosinophils, play a major role in the pathogenesis of atopic dermatitis. Natural killer T (NKT) cells may play a role in atopic dermatitis status. METHODS: The authors examined the percentage of Valpha24+CD161+ NKT cells and CD3+CD16+ CD56+ NKT cells in peripheral blood from 23 patients with atopic dermatitis aged 8 to 35 years (mean, 21.77+/-2.88 years) and 30 healthy controls aged 18 to 32 years (mean, 24.32+/-2.44 years) by using flow cytometric analysis. The mean percentages of Valpha24+CD161+ NKT cell subtypes in the atopic dermatitis group and the healthy group were 0.29%+/-0.02% and 0.42%+/-0.05%, respectively (P<.001). RESULTS: Percentages of Valpha24+CD161+ NKT cell subtypes are significantly lower in patients with atopic dermatitis than healthy individuals. On the other hand, the CD3+CD16+CD56+ NKT cell subtype does not differ between the groups. CONCLUSIONS: The reduction of Valpha24+CD161+ NKT cells subtypes may be involved in the immunopathogenesis of atopic dermatitis.

Procalcitonin is a predictive marker for severe acute pancreatitis.

BACKGROUND: Early identification of patients who develop severe acute pancreatitis and those who can benefit from intensive care is important. We studied whether procalcitonin, a marker of systemic inflammation, is important in the differential diagnosis of patients with mild and severe acute pancreatitis. METHODS: Patients were divided into two groups (mild and severe form) prospectively. Procalcitonin levels and the Ranson's and Acute Physiology and Chronic Health Evaluation II scores were determined both at admission and during the follow-up. RESULTS: Of the 65 patients with acute pancreatitis, 46 had mild and 19 had severe pancreatitis. Sensitivity and specificity values for patients calculated using procalcitonin level at 0.5 ng/ml, Ranson's score at 3 and APACHE II score at 8 cut-off levels, were 100%, 84% and 89%; and 84%, 63% and 89% respectively. CONCLUSION: Procalcitonin is a practical, simple parameter that can be used in order to diagnose severe acute pancreatitis earlier and to monitor the clinical prognosis of the disease.

Serum neopterin levels in patients with chronic hepatitis B.

The aim of this study was to determine the neopterin levels and peripheral blood lymphocyte subgroups in HBeAg-positive and -negative chronic hepatitis B patients. A total of 89 patients were included in the study. The mean serum neopterin level of patients with chronic hepatitis B was significantly higher than that of the control group. In HBeAg-positive chronic hepatitis B patients, the mean serum neopterin level was significantly higher than that of anti-HBeAb-positive patients. There was no significant correlation between the serum neopterin levels and alanine aminotransferase and HBV-DNA levels in HBeAg-positive chronic hepatitis B patients. There were no significant differences between the control subjects and patients with HBeAg-positive or anti-HBeAb-positive hepatitis in terms of the percentage of peripheral blood CD4+ or CD8+ or the ratio of CD4+/CD8+ lymphocytes. Our results suggest an association between elevated neopterin concentrations and HBeAg-positivity in patients with chronic hepatitis B. However, there appears to be no association between the neopterin levels and either hepatocyte damage or viral replication status.

Ibuprofen reduces plasma nitrite/nitrate levels in a rabbit model of endotoxin-induced shock.

OBJECTIVES: The purpose of this study was to investigate the effects of ibuprofen on plasma nitrite/nitrate levels, as indirect indicators of nitric oxide, in correlation with blood pressure in a rabbit model of endotoxin-induced shock. METHODS: A total of 28 rabbits were randomly divided into four groups. Control group received physiological saline, while endotoxin (ETX, E. Coli, 055:B5, 2 mg/kg, i.v.) was administered to the rabbits in the other groups: group II receiving only ETX, in addition to ETX group III received ibuprofen (30 mg/kg) 30 minutes after ETX administration, whilst the group IV received ibuprofen (30 mg/kg) 30 minutes before ETX. Arterial blood pressure and plasma levels of nitrite/nitrate were determined immediately before (time 0) and 30, 60, 90, 120, 180, 240, and 300 minutes after ETX administration. RESULTS: ETX administered groups had significantly higher plasma levels of nitrite/nitrate than the control group, at all consecutive measurements except at time O. Treatment with ibuprofen, either before or after ETX, partly restored the elevated levels of nitrite/nitrate. ETX also caused a significant decrease in blood pressure which was prevented in ibuprofen treated groups. CONCLUSION: Results from this study indicate that administration of ibuprofen prevents sudden reductions in blood pressure by inhibiting excessive production of nitric oxide in rabbit model of endotoxin-induced shock and this may be of importance for providing crucial time for therapeutic intervention and survival in septic shock.

Procalcitonin, c-reactive protein and neopterin levels in patients with coronary atherosclerosis.

OBJECTIVE: Recent studies demonstrate that the serum inflammatory markers increase in patients with atherosclerosis. We aimed to assess whether a difference exists between patients with acute coronary syndrome and patients with stable angina pectoris in respect to serum neopterin, procalcitonin (PCT) and C-reactive protein (CRP) levels. METHODS AND RESULTS: A total of 52 patients (42 male, 10 female) who had atherosclerosis confirmed by angiography and were being followed up for an acute coronary syndrome were recruited and for control group, 45 patients with stable angina pectoris (SA) (35 male and 10 female) who underwent coronary angiography, were examined. Serum concentrations of neopterin, CRP and PCT in the study group (acute coronary syndrome) were compared to control group (stable angina pectoris). The mean neopterin level of the study group was 22.47 +/- 2.93 nmol/l, the mean CRP level was 30.40 +/- 8.05 mg/l and the mean PCT level was 0.40 +/- 0.04 ng/ml. In control group these levels were 12.26 +/- 0.61 nmol/l (p < 0.05), 5.26 +/- 0.64 mg/l (p < 0.001) and 0.19 +/- 0.02 ng/ml (p < 0.001), respectively. CONCLUSION: In the presented study our results showed that these markers can be useful for the assessment of inflammation related to atherosclerosis.

Atorvastatin affects C-reactive protein levels in patients with coronary artery disease.

BACKGROUND: Elevated levels of C-reactive protein (CRP) are considered to be one of the indicators of poor prognosis in coronary artery disease (CAD). The aim of this study was to evaluate anti-inflammatory effects of atorvastatin in patients with CAD by measuring serum CRP levels. METHODS: After measuring the baseline levels of CRP and lipid fractions, the patients were divided into two groups. In Group A (n = 46), atorvastatin (20 mg/day) was administered in addition to classic antianginal treatment (beta-blocker, nitrate and aspirin). In Group B (n = 32), the usual antianginal treatment was continued. Following 4 weeks of treatment the same measurements were repeated. RESULTS: In Group A, CRP decreased from 20.3 mg/dl (95% CI, 9-31.8) to 10.8 mg/dl (95% CI, 2.7-18.9) (p < 0.001). In Group B, CRP decreased from 17 mg/dl (95% CI, 13.1-21) to 12.8 mg/dl (95% CI, 9.7-15.9) (p < 0.01). The decrease in group A was more than in group B (p = 0.003). CONCLUSIONS: In patients with CAD, atorvastatin exerted an anti-inflammatory effect represented by decreasing CRP levels. This effect was independent of the change in low density lipoprotein cholesterol (LDL-C) or high density lipoprotein cholesterol (HDL-C) levels.

C-reactive protein, procalcitonin, interleukin-6, vascular endothelial growth factor and oxidative metabolites in diagnosis of infection and staging in patients with gastric cancer.

AIM: The current study was to determine the serum/plasma levels of VEGF, IL-6, malondialdehyde (MDA), nitric oxide (NO), PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection. METHODS: We examined the levels of serum VEGF, IL-6, PCT, CRP and plasma MDA, NO in 42 preoperative gastric cancer patients and 23 healthy subjects. There were infection anamneses that had no definite origin in 19 cancer patients. RESULTS: The VEGF levels (mean+/-SD; pg/mL) were 478.05+/-178.29 and 473.85+/-131.24 in gastric cancer patients with and without infection, respectively, and these values were not significantly different (P>0.05). The levels of VEGF, CRP, PCT, IL-6, MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP, PCT, IL-6, MDA and NO were statistically increased in infection group when compared with non-infection group (P<0.001). CONCLUSION: Although serum VEGF concentrations were increased in gastric cancer, this increase might not be related to infection. CRP, PCT, IL-6, MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients. These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization. According to the results of this study, IL-6, MDA, NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer.

The effects of intra-operative amiodarone loading on the systemic inflammatory response syndrome induced by cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass (CPB) leads to systemic inflammatory response syndrome (SIRS). In vitro studies showed that amiodarone blocked cytokine production. The aim of this study was to evaluate the effect of intra-operative amiodarone loading on SIRS. METHODS: This prospective randomized study included 24 patients who underwent on-pump coronary artery surgery. The patients were classified into control (n=12) and amiodarone (n=12) groups. Plasma levels of the pro-inflammatory (C-reactive protein - CRP, interleukin-6 - IL-6) and the anti-inflammatory markers (interleukin-10 - IL-10) were measured before the induction of anesthesia, 5 minutes after aortic declamping, after protamine administration and 24 hours after the CPB. The myocardial lactate production was calculated before CPB and 5 minutes after aortic declamping. Statistical analyses were performed using Mann-Whitney U, Fischer's exact and ANOVA tests. RESULTS: In both groups, the IL-6 levels significantly increased after declamping (91.18+/-16.27 pg/ml and 86.37+/-14.66 pg/ml, p<0.01) and reached peak values after infusion of protamine (329.07+/-32.24 pg/ml and 354.31+/-29.61 pg/ml, p<0.01). The highest values of IL-10 were detected after infusion of protamine in the control and amiodarone groups (265.58+/-85.63 pg/ml, p<0.01 and 287.44+/-65.26 pg/ml, p<0.01). Amiodarone did not have any significant effect on release of cytokines. The CRP levels were significantly elevated in both groups at 24th hour after CPB, but no significant difference was found between the groups. Compared with pre-CPB values, lactate production increased significantly in two groups after aortic declamping. However there was no significant difference between the groups. CONCLUSION: The results indicate that intraoperative loading of amiodarone, which is used for atrial fibrillation prophylaxis, does not seem to alter inflammatory response during CPB.

Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis and Behçet's disease.

Rheumatoid arthritis (RA) is associated with progressive joint destruction and disability. Early diagnosis of RA is important, since early and aggressive treatments lead to a better outcome. Circulating autoantibodies are a serological hallmark of systemic rheumatic diseases. More recently, antibodies directed to a cyclic citrullinated peptide, anti-CCP antibodies, have been established as specific diagnostic and prognostic tools for RA. The aims of this study were to assess the diagnostic and radiological prognostic value of the anti-CCP antibody in Turkish patients with RA (n = 97) and those with Behçet's disease (BD) (n = 46). The study also included 35 healthy controls. Anti-CCP antibodies were measured by ELISA, and radiological damage was evaluated by using modified Larsen scoring. In the RA group, sensitivity and specificity were 80.4% and 93.5% for rheumatoid factor (RF), and 74.2% and 97.8% for anti-CCP antibody, respectively. RF was positive in 3 BD patients (6.5%) and in one of the controls (2.9%). In contrast, anti-CCP antibodies were detected in one BD patient (2.2%), but not in the control subjects. Deformed joint counts and radiographic scores were higher in anti-CCP antibody-positive RA patients (n = 72) than those in anti-CCP antibody-negative patients (n = 25) (p < 0.05). Moreover, anti-CCP antibody titer correlated with deformed joint count (r = 0.224, p < 0.05) and radiographic score (r = 0.308, p < 0.05). This study indicates the diagnostic and prognostic utility of anti-CCP antibodies in Turkish patients with RA. Importantly, anti-CCP antibodies are not associated with BD.

Serum interleukin-2 and neopterin levels as useful markers for treatment of active pulmonary tuberculosis.

Macrophages and T cells are responsible for the main immune response to tuberculosis by secreting many cytokines and other substances. The aim of this study was to determine the effects of multidrug treatment on serum levels of interleukin-2 (IL-2), secreted by activated T cells, and of neopterin, secreted by macrophages and monocytes, in patients with pulmonary tuberculosis. The study included 30 patients with active pulmonary tuberculosis, confirmed by the detection of acid-fast bacilli in direct sputum smears and/or sputum cultures. The serum levels of IL-2 and neopterin were measured before and during the treatment and compared with 15 patients with inactive pulmonary tuberculosis and 15 healthy controls. Serum IL-2 and neopterin levels were higher in patients with active tuberculosis (164.53 +/- 58.91 pg/ml and 69.54 +/- 29.42 nmol/l, respectively) than those in inactive tuberculosis (95.43 +/- 31.17 pg/ml and 10.71 +/- 1.78 nmol/l) or controls (79.20 +/- 14.81 pg/ml and 9.50 +/- 2.27 nmol/l) (p < 0.001 for each parameter). No significant differences were found in IL-2 and neopterin levels between inactive tuberculosis and control subjects. The IL-2 levels remained elevated in active tuberculosis at 2nd month of treatment (p < 0.001) and decreased to the control levels after 4th month. Neopterin levels were significantly higher in active tuberculosis than those in inactive tuberculosis or controls at the 2nd and 4th months of treatment. These findings indicate that measurements of serum IL-2 and neopterin levels are useful in following up the treatment and immune response to tuberculosis.

Predictive value of procalcitonin for the diagnosis of bowel strangulation.

Intestinal obstruction is responsible for 3% of admissions to hospital emergency surgical departments, but it is difficult to distinguish simple obstruction from strangulation. Simple criteria for this distinction are sought. In this experimental study, procalcitonin, a known marker of bacterial inflammation, was used to detect strangulation. The predictive value of procalcitonin for small bowel strangulation was evaluated. Thirty male New Zealand rabbits (mean weight: 3.0 kg) were divided into three groups. In the first (control) group, only laparatomy was performed. In the second group, simple obstruction was created by ligating a 10-cm distal ileum segment. In the third group, distal strangulation was created by ligating a 10-cm distal ileum segment with the mesentery. Blood (1 cc) was taken from the right auricular vein of each animal for measuring the procalcitonin level. In both the control group and the simple obstruction group the procalcitonin levels were normal. In the strangulation group, elevation of procalcitonin was detected after 30 minutes, and the elevation was statistically significant at 120th minute compared with the control and simple obstruction groups. In patients with small bowel obstruction, measurement of procalcitonin levels is easy to perform and can be used in the follow-up. A more extensive clinical study is needed to evaluate the accuracy of the test as a marker.

Serum procalcitonin and cerebrospinal fluid cytokines level in children with meningitis.

AIMS: To determine the level of serum procalcitonin and cerebrospinal fluid cytokines in children with bacterial or viral meningitis and to document the use of these parameters in differential diagnosis. RESULTS: Before the start of antibiotic treatment, serum procalcitonin and tumor necrosis factor alpha levels were found to be higher in acute bacterial meningitis compared with viral meningitis and with the control group. Similarly, cerebrospinal fluid interleukin-6 levels were found to be significantly higher in children with acute bacterial meningitis compared with viral meningitis. However, no significant difference was determined between groups in respect to the cerebrospinal fluid interleukin-8 level. CONCLUSION: Serum procalcitonin and cerebrospinal fluid tumor necrosis factor alpha levels can be used in the early diagnosis of bacterial meningitis. Similarly, they may be useful adjuncts in differential diagnosis of bacterial and viral meningitis.