Alterations in immune cell subsets and their cytokine secretion profile in childhood idiopathic thrombocytopenic purpura (ITP)

Immune thrombocytopenic purpura (ITP) is acquired autoimmune disease in children characterized by the breakdown of immune tolerance. This work is designed to explore the contribution of different lymphocyte subsets in acute and chronic ITP children. Imbalance in the T helper type 1 (Th1)/Th2 cytokine secretion profile was investigated. The frequency of T (CD3⁺, CD4⁺, CD8⁺) and B (CD19⁺) lymphocytes, natural killer (NK) (CD16⁺56⁺) and regulatory T (T_reg) [CD4⁺CD25^+highforkhead box protein 3 (FoxP3)⁺] cells was investigated by flow cytometry in 35 ITP children (15 acute and 20 chronic) and 10 healthy controls. Plasma levels of Th1 cytokines [interferon (IFN-γ) and tumour necrosis factor (TNF-α)] and Th2 [interleukin (IL)-4, IL-6 and IL-10)] cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The percentage of T_reg (P < 0·001) and natural killer (NK) (P < 0·001) cells were significantly decreased in ITP patients compared to healthy controls. A negative correlation was reported between the percentage of T_reg cells and development of acute (r = −0·737; P < 0·01) and chronic (r = −0·515; P < 0·01) disease. All evaluated cytokines (IFN-γ, TNF-α, IL-4, IL-6 and IL-10) were elevated significantly in ITP patients (P < 0·001, P < 0·05, P < 0·05, P < 0·05 and P < 0·001, respectively) compared to controls. In conclusion, our data shed some light on the fundamental role of immune cells and their related cytokines in ITP patients. The loss of tolerance in ITP may contribute to the dysfunction of T_regs. Understanding the role of T cell subsets will permit a better control of autoimmunity through manipulation of their cytokine network.     

Emulsified isoflurane preconditioning reduces lung injury induced by hepatic ischemia/reperfusion in rats

Objective: To investigate whether emulsified isoflurane preconditioning could reduce lung injury induced by hepatic I/R in rats and its mechanism.Materials and methods: 32 pentobarbital-anesthetized Sprague-Dawley rats were equally randomized into four groups: laparotomy group (Sham group), hepatic I/R and normal saline infusion group (I/R+S group), I/R and lipid vehicle infusion (I/R+V group), or I/R and 8% emulsified isoflurane infusion (I/R+E group) at the rate of 8 ml·kg^-1·h^-1 for 30 min. Blood supply of the hepatic artery and portal vein to the left and the median liver lobes was occluded for 90 min after 30-min washout time. Reperfusion was allowed to proceed for 4 h before sacrifice of the animals. Lung injury was observed histologically. Neutrophil infiltration and TNF-α concentration in serum and lung were measured. Changes of wet-to-dry weight ratios in lung tissue, ICAM-1 expression and NF-κB activity in lung after hepatic I/R were determined.Results: Compared with I/R+S or I/R+V group, emulsified isoflurane preconditioning reduced hepatic I/R-induced lung histologic injury and inhibited the increase of myeloperoxidase (MPO) activity in the lung tissue markedly (5.5±1.37 and 5.22±1.33 vs 3.81±1.62 U/g, P<0.05). In addition, both serum and lung tissue TNF-α levels were reduced in I/R+E group (104.58±31.40 and 94.60±22.23 vs 72.44±17.28 pg/ml, P<0.05; 393.51±88.22 and 405.46±102.87 vs 292.62±74.56 pg/ml, P<0.01). Emulsified isoflurane preconditioning also inhibited the increase of ICAM-1 expression (0.79±0.17 and 0.84±0.24 vs 0.62±0.21, P<0.05) and NF-κB translocation (4.93±0.48 and 4.76±0.57 vs 4.01±0.86, P<0.05) in the lung tissue markedly.Conclusions: Emulsified isoflurane preconditioning markedly attenuated hepatic I/R-induced lung injury in rats, which may be hopefully applied to the clinical treatment of organ injury caused by hepatic surgery, transplantation or hemorrhagic shock.     

Assessment of indicators of vitamin A status in non-cirrhotic chronic hepatitis C patients

Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels.     

Concentrations of connective tissue growth factor in patients with nonalcoholic fatty liver disease: Association with liver fibrosis

Aim: In this study, we aimed to investigate the relationship between the histological fibrosis stage of nonalcoholic fatty liver disease (NAFLD) and serum connective tissue growth factor (CTGF) to determine the usefulness of this relationship in clinical practice. Methods: Serum samples were collected from 51 patients with biopsy-proven NAFLD and 28 healthy controls, and serum levels of CTGF were assayed by ELISA. Results: Levels of CTGF were significantly higher in patients with NAFLD compared with controls (P=0.001). The serum CTGF levels were significantly increased, that correlated with histological fibrosis stage, in patients with NAFLD [in patients with no fibrosis (stage 0) 308.2 ± 142.9, with mild fibrosis (stage 1-2) 519.9 ± 375.2 and with advanced fibrosis (stage 3-4) 1353.2 ± 610 ng/l, P < 0.001]. Also serum level of CTGF was found as an independent predictor of histological fibrosis stage in patients with NAFLD (β = 0.662, t=5.6, P <0.001). The area under the ROC curve was estimated 0.931 to separate patients with severe fibrosis from patients with other fibrotic stages. Conclusion: Serum levels of CTGF may be a clinical utility for distinguishing NAFLD patients with and without advanced fibrosis.     

Changes in plasma lipid concentrations and risk of coronary artery disease in army veterans suffering from chronic posttraumatic stress disorder

Aim

To test the differences in serum lipid concentrations between veterans with chronic posttraumatic stress disorder (PTSD) and veterans without PTSD.

Methods

We determined plasma lipid parameters and calculated risk factors for 50 veterans in the PTSD group and 50 veterans in the non-PTSD group. Trauma exposure, coping strategies, and quality of life were assessed with Life Stressor List, Manchester Short Assessment of Quality of Life Scale, and Folkman-Lazarus Coping Strategies Questionnaire.

Results

There was no difference between the groups in the exposure to combat trauma. PTSD group had significantly lover education than non-PTSD group (10.6 ± 1.8 vs 12.4 ± 2.6 years, P = 0.007) and lower monthly income per family member (€67.8 ± 51.3 vs €281.9 ± 208.2, P < 0.001). PTSD group had significantly higher levels of all plasma lipid parameters (cholesterol: 6.54 ± 1.24 vs 5.40 ± 1.09 mmol/L, P < 0.001; triglycerides: 2.55 ± 0.68 vs 1.73 ± 0.77 mmol/L, P < 0.001; very low density lipoprotein-cholesterol: 1.14 ± 0.32 vs 0.78 ± 0.35 mmol/L, P < 0.001; low density lipoprotein-cholesterol: 4.49 ± 1.06 vs 3.46 ± 0.93 mmol/L, P < 0.001). High-density lipoprotein cholesterol concentration was significantly lower in PTSD group (0.96 ± 0.18 vs 1.15 ± 0.24 mmol/L, P < 0.001). Established risk factor for arteriosclerosis (6.96 ± 1.19 vs 4.71 ± 0.88, P < 0.001) and Adult Treatment Panel III ten years risk for coronary disease (19.44 ± 7.27% vs 9.74 ± 4.10%, P < 0.001) were significantly higher in the PTSD group. Secondary traumatization was significantly more frequent in the PTSD group (3.8 ± 5.7 vs 1.3 ± 4.7 events; P < 0.001).

Conclusions

Chronic PTSD is associated with dyslipidemia, leading to an increased risk of coronary artery disease. Environmental factors and coping strategies should be considered as important factors for the occurrence and persistence of PTSD.“The body keeps the score: memory and the evolving psychobiology of post traumatic stress” by Bessel van der Kolk (1) was published in the Harvard Review of Psychiatry in 1994. Although it may not be the first article on neurobiology of posttraumatic stress disorder (PTSD), the strong metaphor contained in the first part of its title summarizes the research results in this field. Studies looking for biological causes of a disorder that is clearly precipitated by environmental or man-made causes were largely outnumbered by studies on the psychosocial nature of the disorder decades after the delayed first recognition of PTSD in the diagnostic manuals – 1980 in Diagnostic and Statistical Manual of Mental Disorders III (DSM III) (2) and 1990 in the International Classification of Diseases-10 (ICD-10) (3). A small number of studies appeared in literature in parallel with the recognition of the disorder, but the number of biological studies since September 11, 2001 has grown 5-fold and keeps growing (4).Research interest mainly focused on alterations of neuroendocrine regulation (5,6) and neuroanatomical (7) and neuroimmunological alterations (8,9). From the neuroendocrine point of view, in PTSD there is an increased noradrenergic activity in absence of shutdown by serum cortisol that has been found to be decreased in this disorder due to dysregulation of the hypothalamo-pituitary-adrenal axis (10-12). Studies on changes in serum lipid concentrations were based on clinical observations and the results of epidemiological studies indicating increased cerebrovascular and cardiovascular morbidity and mortality in survivors of prolonged traumatic and combat stress (13-17). Kagan’s pioneer study (18) of changes in lipid status of Vietnam veterans was published in 1999 and was followed by the work of other researchers who confirmed its results (19-23).The population of Bosnia and Herzegovina suffered massive and prolonged traumatization in the 1992-1995 war (24-26). Increase in the prevalence and incidence of PTSD in comparison with the period before the war, as well as the increase in trauma-related disorders in overall psychiatric morbidity, represents a logical consequence of these events (27). In our work with people suffering from chronic PTSD, we had frequently noticed alterations of serum lipids, associated with an increased risk of cardiovascular diseases. This is consistent with our clinical observation of increased cardiovascular and cerebrovascular morbidity in patients who had been treated in the Unit for Trauma-related Disorders of the Department of Psychiatry of the University Clinical Center in Sarajevo and the literature (13-17). Therefore, we aimed to explore the differences in concentrations of serum cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), index of arteriosclerosis, established risk factor for arteriosclerosis (ERF), and 10 years-risk for coronary disease according to Adult Treatment Panel III (ATP III) (28) between veterans with the diagnosis of chronic PTSD and veterans without the diagnosis of PTSD. Our second aim was to compare and analyze the differences between the two groups in socio-demographic characteristics, trauma exposure measures, secondary traumatization (after the war), PTSD symptoms, coping strategies, and quality of life, to obtain information on the factors influencing the development and persistence of PTSD in veterans with combat stress exposure.There are divided opinions in literature whether this disorder develops in individuals with certain predisposing factors or all people have equal chances of developing PTSD (29-32). There is also a question whether biological markers of PTSD are trait markers or state markers, as well as whether PTSD can be explained by stress-diathesis model as schizophrenia (33). To explore these claims, we also compared socio-demographic characteristics of the sample, trauma events inventory, coping strategies, and quality of life indicators.     

Reduced plasma adiponectin levels relative to oxidized low density lipoprotein and nitric oxide in coronary artery disease patients

INTRODUCTION:

Adiponectin is a circulating hormone that is produced exclusively by adipocytes and has anti-inflammatory and anti-atherogenic properties. The hypothesis that there are differences in adiponectin levels between stable and unstable coronary-artery disease patients remains controversial. Furthermore, the potential relationships between the plasma adiponectin level and the inflammatory and non-inflammatory markers (oxidized low density lipoprotein and nitric oxide) in patients with stable and unstable coronary-artery disease relative to normal subjects have not been assessed.

OBJECTIVES:

To assess whether plasma adiponectin levels differ among patients with stable and unstable coronary-artery disease and among control subjects, and to correlate plasma adiponectin level with inflammatory and clinical risk factors (such as oxidized-LDL and nitric oxide) in these patients.

METHODS:

This study included 50 control subjects, 50 stable angina patients and 50 unstable angina patients with angiographically documented coronary-artery disease. Plasma adiponectin and oxidized-LDL levels were determined using an enzyme immunoassay. Plasma nitric oxide, high sensitivity C-reactive protein and lipid profile levels were also measured.

RESULTS:

Plasma adiponectin levels were lower in the unstable angina patients (4.9±1.30 µg/mL) than in the stable angina patients (6.34±1.0 µg/mL) or in the controls (9.25±1.8 µg/mL); these levels were also significantly lower in stable angina patients versus controls (p<0.001). Plasma adiponectin levels were negatively correlated with oxidized-LDL, high sensitivity C-reactive protein, lipid profile and other clinical risk factors but positively correlated with nitric oxide.

CONCLUSION:

Plasma adiponectin levels were found to be lower in both stable and unstable angina patients relative to control subjects, and the correlation between plasma adiponectin and cardiovascular markers is weakened in these patients.     

Curative Resection of Hepatocellualr Carcinoma Using Modified Glissonean Pedicle Transection versus the Pringle Maneuver: A Case Control Study

Objective: The Glissonean pedicle transection method of liver resection has been found to shorten operative time and minimize intraoperative bleeding during liver segmentectomy. We have compared the feasibility, effectiveness, and safety of the Glissonean pedicle transection method with the Pringle maneuver in patients undergoing selective curative resection of large hepatocellualr carcinoma (HCC).Methods: Eligible patients with large (> 5 cm) nodular HCC (n = 50) were assigned to undergo curative hepatectomy using the Glissonean pedicle transection method (n = 25) or the Pringle maneuver (n = 25). Partial interruption of the infrahepatic inferior vena cava was incorporated to further reduce bleeding from liver transection. The primary outcome measure was postoperative changes in liver function from baseline. Secondary outcomes included operating time, volume of intraoperative blood loss/transfusion, and time to resolution of ascites.Results: The two groups were comparable in age, sex, site and size of the liver tumor, segment or lobe intended to be resected, and liver function reserve, and the results were not significant statistically. All patients underwent successful major hepatectomies using the assigned method, with the extent of major hepatectomy comparable in the two groups (P = 0.832). The Glissonean approach was associated with shorter hepatic inflow interruption (30.0 ± 12.0 min vs. 45.0 ± 13.0 min, P < 0.001), lower volume of blood loss (145.0 ± 20.0 mL vs. 298.0 ± 109.0 mL, P < 0.001), reduced requirement for transfusion (0.0 ± 0.0 mL vs. 200.0 ± 109.0 mL, P < 0.0001), and more rapid resolution of ascites (9.5 ± 1.2 d vs. 15.3 ± 2.4 d, P < 0.001). Postoperative liver function measures were comparable in the two groups, and the results were not significant statistically.Conclusion: The Glissonean pedicle transection method is a feasible, effective, and safe technique for hepatic inflow control during the curative resection of large nodular HCCs.     

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease

Background/Aims

The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH.

Methods

One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea.

Results

According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH.

Conclusions

Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.     

Serum levels of platelet released CD40 ligand are increased in early onset occlusive carotid artery disease

Objective: Soluble CD40 ligand (sCD40L) has been suggested as a key mediator between inflammation and atherosclerosis, and the CD40-CD40L interaction has a role in atherosclerotic lesion progression. We evaluated if platelet released serum sCD40L and sCD40 levels differ between patients with early onset occlusive carotid artery disease and age-matched controls. Methods: sCD40L and sCD40 levels were measured in serum samples of 60 patients with occlusive carotid artery disease and 30 age-matched controls using ELISA. Degree of stenosis of the internal carotid artery (ICA), and intima-media thickness (IMT) in the common carotid artery were measured by high resolution ultrasound. Values are given as mean ± SD. Results: Mean age was 50.9 ± 3.5 and 50.1 ± 3.5 years in the patient and control groups. IMT was significantly thicker in patients than in controls (0.89 ± 0.14 vs. 0.78 ±0.12 mm, p = 0.0003). Serum levels of sCD40L were significantly higher (6.9 ± 5 vs. 4.5 ± 3.0 ng/mL, p = 0.038) in patients, whereas sCD40 did not differ significantly between patients and controls (85 ± 56.9 vs. 79.3 ± 18.7 pg/mL, p = 0.34). IMT did not correlate with sCD40L or sCD40 levels (R = −0.03, p = 0.77; and R = 0.109, p = 0.308, respectively). Conclusions: sCD40L but not sCD40 levels are significantly higher in patients with occlusive carotid artery disease. Platelet derived sCD40L may be a key mediator among inflammation, thrombosis and atherosclerosis.     

Low ficolin-2 levels in common variable immunodeficiency patients with bronchiectasis

Common variable immunodeficiency (CVID) encompasses a heterogeneous group of antibody deficiencies characterized by susceptibility to recurrent infections and sequelae, including bronchiectasis. We investigated the relevance of the lectin complement pathway in CVID patients by analysing ficolin-2 and ficolin-3 serum levels and genotyping single nucleotide polymorphisms (SNPs) in the FCN2 and FCN3 genes. Our results show that ficolin-2 levels in CVID patients are significantly lower (P < 0·0001) than in controls. The lowest ficolin-2 levels are found in CVID patients with bronchiectasis (P = 0·0004) and autoimmunity (P = 0·04). Although serum levels of ficolin-3 were similar in CVID patients and controls, CVID patients with bronchiectasis again showed lower levels when compared to controls (P = 0·0001). Analysis of single nucleotide polymorphisms in the FCN2 gene confirmed known influences on ficolin-2 serum levels, but did not support a genetic basis for the observed ficolin-2 deficiency in CVID. We found that CVID patients with bronchiectasis have very low levels of ficolin-2. The reason for the deficiency of ficolin-2 in CVID and any possible causal relationship is currently unknown. However, as bronchiectasis is a very important factor for morbidity and mortality in CVID, ficolin-2 could also serve as biomarker for monitoring disease complications such as bronchiectasis.     

Sexual functioning in war veterans with posttraumatic stress disorder

Aim

To assess the sexual dysfunction among Croatian war veterans with combat-related posttraumatic stress disorder (PTSD).

Method

The study included two groups – 101 war veterans with PTSD and 55 healthy control volunteers receiving outpatient general health care in several outpatient clinics in Split. tructured interviews on different aspects of sexual functioning were conducted from April to October 2007 by trained interviewers.

Results

Respondents with PTSD reported significantly less sexual activity during the previous month than controls (sexual fantasies 2.5 ± 1.6 vs 3.7 ± 1.7, P<0.001; foreplay 2.4 ± 1.6 vs 3.5 ± 1.6, P<0.001; oral sex 1.6 ± 1.2 vs 2.6 ± 1.5, P<0.001; and sexual intercourse 2.4 ± 1.6 vs 3.8 ± 1.5, P<0.001) on a 7-point Likert type scale (from 1 – not a single time to 7 – more times a day). As reasons for reduced sexual activities, respondents with PTSD more frequently than controls reported their own health problems (3.2 ± 1.2 vs 1.5 ± 0.8; P<0.001) or health problems of their partner (2.4 ± 1.1 vs 1.9 ± 1.1; P = 0.004), whereas controls more frequently reported overwork than respondents with PTSD (2.6 ± 1.1 vs 2.1 ± 1.0; P = 0.007) on a 5-point Likert type scale (from 1 – not a single time to 5 – always). Respondents with PTSD reported antidepressant (n = 52, 51%) or anxyolitics use (n = 73, 72.3%). In a subgroup analysis, respondents with PTSD who were taking antidepressants masturbated less frequently than those who were not taking them (1.9 ± 1.3 vs 2.5 ± 1.6; P = 0.039), whereas premature ejaculation was more often experienced by respondents with PTSD who were not taking antidepressants than by those who were taking them (3.5 ± 1.8 vs 2.7 ± 1.5; P<0.049) both on a 7-point Likert type scale (from1 – not a single time to 7 – more times a day).

Conclusion

War veterans with PTSD had less sexual activity, hypoactive sexual desire, and erectile difficulties. Antidepressant therapy in veterans with PTSD may be associated with hypoactive sexual desire.Posttraumatic stress disorder (PTSD) is a complex phenomenon that develops as a response to a psychological trauma and affects several levels of personality, causing changes in both mental and physical functioning (1-3). It is often associated with problems in interpersonal relationships and difficulties with attachment, intimacy, and sexuality (1,2). Problems in the realm of sexuality arise from the individual’s inability to establish an adequate emotional-physical relationship with the partner, as well as from the disturbances in mental and physical health (4). Several studies found that the prevalence of sexual dysfunctions among patients with PTSD was higher than in general population (5-7). Dysfunctions can occur in almost all domains of sexuality – activity, desire, arousal, orgasm, and satisfaction with sexual life (5). The most frequent difficulties are erectile dysfunction and premature ejaculation (6,7). Antidepressant therapy is an additional factor that can aggravate difficulties in sexual functioning (8).Sexual dysfunctions in Croatia have rarely been explored (4,9). A national study that explored the prevalence and risk factors of erectile and ejaculatory difficulties pointed out the role of anxiety and stress in the occurrence of premature ejaculation (4). The significance of sexuality for one’s perception of quality of life, a high prevalence of PTSD in a post-war society such as Croatia, and a lack of relevant studies all point to the importance of studying this domain of veterans’ life (10,11). Our aim was to assess the impact of PTSD on the occurrence of sexual dysfunctions.     

Heparin‐coated cardiopulmonary bypass circuits selectively deplete the pattern recognition molecule ficolin‐2 of the lectin complement pathway in vivo

The complement system can be activated via the lectin pathway by the recognition molecules mannose-binding lectin (MBL) and the ficolins. Ficolin-2 exhibits binding against a broad range of ligands, including biomaterials in vitro, and low ficolin-2 levels are associated with increased risk of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits. Bloods were drawn at five time-points before, during and postoperatively from 30 patients undergoing elective cardiac surgery. Patients were randomized into two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosphorylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, ficolin-1, −2 and −3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured. Ficolin-3-mediated complement activation potential was evaluated with C4, C3 and TCC as output. There was no significant difference between the two circuit materials regarding MBL, ficolin-1 and −3. In the Bioline® group the ficolin-2 levels decreased significantly after initiation of surgery (P < 0·0001) and remained reduced throughout the sampling period. This was not seen for Phisio®-coated circuits. Ficolin-3-mediated complement activation potential was reduced significantly in both groups after start of operation (P < 0·0001), whereas soluble C3a and TCC in the samples were increased (P < 0·0001). Ficolin-2 was depleted from plasma during cardiac surgery when using heparin-coated bypass circuits and did not reach baseline level 24 h postoperation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures.     

Immunoglobulin A in serum: an old acquaintance as a new prognostic biomarker in idiopathic pulmonary fibrosis

Immunoglobulin (Ig)A is an important immunoglobulin in mucosal immunity and protects the lungs against invading pathogens. The production of IgA is regulated by transforming growth factor (TGF)-β, a versatile cytokine and key player in the pathogenesis of pulmonary fibrosis. TGF-β is up-regulated in patients with idiopathic pulmonary fibrosis (IPF), but difficult to use as a biomarker. The aim of this study was to evaluate the prognostic value of IgA in serum in patients with IPF. We examined IgA levels at time of diagnosis in 86 patients diagnosed with IPF. Mean serum IgA level in IPF is 3·22 g/l and regression analyses showed a significant association with mortality (hazard ratio = 1·445, P = 0·002). A significantly worse survival was found in patients with IgA serum levels > 2·85 g/l compared to patients with lower IgA serum levels (P = 0·003). These findings were confirmed in a duplication cohort. In conclusion, the level of IgA in blood is a promising prognostic marker in IPF and can be implemented easily in the hospital setting. Future studies are warranted to investigate if repeated measurements of serum IgA can further improve the performance of serum IgA as a prognostic marker.     

Plasma B-type Natriuretic Peptide Level in Patients with Acute Cerebral Infarction according to Infarction Subtype and Infarction Volume

Background: Plasma B-type natriuretic peptide (BNP) is used as a diagnostic marker of cardiovascular diseases. BNP is secreted mainly from the myocardium and has been detected by immunoreactivity in brain and cerebral arteries. The aim of our study was to investigate plasma BNP in patients with acute cerebral infarction according to infarction subtype and infarction volume.Methods: We studied 141 patients with acute cerebral infarction, classified as large artery atherosclerosis (LAA), cardioembolism (CE), or small vessel disease (SA) according to the Trial of Org 10172 in Acute Stroke Treatment classification. Plasma BNP level was measured in patients and 61 healthy controls. We analyzed various clinical and laboratory variables of patients according to plasma BNP level.Results: Compared to controls, the patients had higher plasma BNP (11.9 ± 11.7 pg/mL versus 124.6 ± 228.8 pg/mL, p <0.01). The highest quartile BNP group was associated with advanced age, female gender, current non-smoker, atrial fibrillation, heart failure, CE group, increased white blood cell counts, increased high sensitivity C-reactive protein, increased left atrium size, decreased left ventricular ejection fraction, increased initial National Institute of Health Stroke Scale, and increased infarction volume. According to multiple regression analysis, CE group, female gender, and infarction volume were independently associated with plasma BNP. Plasma BNP level showed statistically significant differences among LAA (n = 71), CE (n = 50), and SA (n = 20) groups (p <0.001), and the expression decreased in order of CE (253.8 ± 337.1 pg/mL), LAA (61.6 ± 78.8 pg/mL), and SA (25.3 ± 24.8 pg/mL). Increased plasma BNP correlated with increased infarction volume (r = 0.42, p <0.001).Conclusions: Plasma BNP may be helpful for prediction of etiologic classification of acute cerebral infarction and infarction volume.     

Taiwanese female vegetarians have lower lipoprotein-associated phospholipase A2 compared with omnivores

Purpose

Many studies supported that vegetarians have a lower risk of cardiac diseases and mortality, partly due to better blood pressure and serum cholesterol profiles. However, the inflammatory markers, especially lipoprotein-associated phospholipase A2 (Lp-PLA2), have not been well-studied. This study aimed to compare inflammatory markers and conventional risk factors between vegetarians and omnivores.

Materials and Methods

One hundred and seventy-three vegetarians and 190 omnivores were studied. Fasting blood samples were obtained to compare levels of glucose, total cholesterol, triacylglycerol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, homocysteine, Lp-PLA2 activity, and high-sensitivity C-reactive protein (hs-CRP).

Results

Vegetarians had higher serum levels of the following markers: hs-CRP (1.8 ± 3.4 vs. 1.2 1.8 mg/L, respectively; p = 0.05), homocysteine (9.39 ± 3.22 vs. 7.62 ± 2.41 µmol/L, respectively; p < 0.01), and triacylglycerol (96.91 ± 59.56 vs. 84.66 ± 43.24 mg/dL, respectively; p < 0.05). Vegetarians also had lower levels of Lp-PLA2 (18.32 ± 7.19 10-3 µmol/min/mL vs. 20.22 8.13 10-3 µmol/min/mL; p < 0.05), total cholesterol (180.62 ± 36.55 mg/dL vs. 192.73 ± 36.57 mg/dL; p < 0.01), LDL cholesterol (118.15 ± 32.8 vs. 126.41 ± 34.28 mg/dL; p < 0.05), and HDL cholesterol (55.59 ± 13.30 vs. 62.09 ± 14.52 mg/dL, p < 0.01). Multivariate analyses demonstrated that a vegetarian diet increases the chances for high serum hs-CRP and low Lp-PLA2 activity.

Conclusion

In addition to lower total cholesterol, LDL-cholesterol, and HDL-cholesterol, Taiwanese female vegetarians have lower serum Lp-PLA2 activity but higher levels of hs-CRP, homocysteine, and triacylglyerol. It might be due to geographic differences of vegetarian diets, and further studies are needed.     

Increased Transforming Growth Factor-beta1 in Alcohol Dependence

Ethanol and its metabolite acetaldehyde increase transforming growth factor beta1 (TGF-β1) expression in animal studies. TGF-β1 is related with the hepatic stellate cell (the key element of hepatic fibrogenesis) and the radial glia (the key element of neuronal migration). Blood samples were collected from 41 patients with alcohol dependence, TGF-β1 levels measured by ELISA were compared with 41 normal subjects. Plasma TGF-β1 levels in the patients with alcohol dependence (1,653.11±532.45 pg/mL) were significantly higher than those of healthy subjects (669.87±366.53 pg/mL) (P=0.000). Patients with or without liver pathology showed no difference in TGF-β1 (P=0.36). Increased TGF-β1 may mediate deleterious effect of alcohol such as hepatic fibrosis and suppressed neuronal developments in alcohol dependence patients.     

Serum Level of Interleukin-33 and Soluble ST2 and Their Association with Disease Activity in Patients with Behcet's Disease

Interleukin (IL)-33 is an important mediator of innate immunity. Behcet''s disease (BD) is an autoinflammatory disorder characterized by hyperactivity of the innate immune response. We measured serum levels of IL-33 and its receptor soluble ST2 (sST2) in patients with BD to investigate their association with disease activity. Serum levels of both IL-33 and sST2 were higher in patients with BD compared with those in normal controls (IL-33: 594.48±175.04 pg/mL in BD and 224.23±56.64 pg/mL in normal controls [P=0.048], sST2: 99.01±15.92 pg/mL in BD and 23.56±3.25 pg/mL in normal controls [P<0.001]). IL-33 and sST2 expression in skin tissue, as shown by immunohistochemistry, was higher in patients with BD compared with that in the normal controls. Serum sST2 level correlated significantly with the BD currently active form (BDCAF), Iranian BD dynamic activity measure (IBDDAM), erythrocyte sedimentation rate and C-reactive protein. Multiple linear regression showed that serum sST2 was an independent factor associated with IBBDAM (regression coefficient, 0.374; P=0.004), and BDCAF (regression coefficient, 0.236; P=0.047). These results demonstrate that IL-33 and sST2 are highly expressed in patients with BD and that serum sST2 is an independent factor associated with IBDDAM and BDCAF, suggesting a potential role for sST2 as a surrogate marker of disease activity in patients with BD.     

Increased Serum Cathepsin K in Patients with Coronary Artery Disease

Purpose

Cathepsin K is a potent collagenase implicated in human and animal atherosclerosis-based vascular remodeling. This study examined the hypothesis that serum CatK is associated with the prevalence of coronary artery disease (CAD).

Materials and Methods

Between January 2011 and December 2012, 256 consecutive subjects were enrolled from among patients who underwent coronary angiography and percutaneous coronary intervention treatment. A total of 129 age-matched subjects served as controls.

Results

The subjects'' serum cathepsin K and high sensitive C-reactive protein (hs-CRP) and high-density lipoprotein cholesterol were measured. The patients with CAD had significantly higher serum cathepsin K levels compared to the controls (130.8±25.5 ng/mL vs. 86.9±25.5 ng/mL, p<0.001), and the patients with acute coronary syndrome had significantly higher serum cathepsin K levels compared to those with stable angina pectoris (137.1±26.9 ng/mL vs. 102.6±12.9 ng/mL, p<0.001). A linear regression analysis showed that overall, the cathepsin K levels were inversely correlated with the high-density lipoprotein levels (r=-0.29, p<0.01) and positively with hs-CRP levels (r=0.32, p<0.01). Multiple logistic regression analyses shows that cathepsin K levels were independent predictors of CAD (odds ratio, 1.76; 95% confidence interval, 1.12 to 1.56; p<0.01).

Conclusion

These data indicated that elevated levels of cathepsin K are closely associated with the presence of CAD and that circulating cathepsin K serves a useful biomarker for CAD.