Ctirad Andrýs

Markers of thrombogenesis are activated in unmedicated patients with acute psychosis: a matched case control study.

BackgroundAntipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism in schizophrenia. The extent to which the propensity for venous thromboembolism is linked to antipsychotic medication alone or psychosis itself is unclear. The objective of this study was to determine whether markers of thrombogenesis are increased in psychotic patients who have not yet been treated with antipsychotic medication.MethodsWe investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of fourteen men and eleven women with acute psychosis (age 29.1 ± 8.3 years, body mass index 23.6 ± 4.7), and twenty-five healthy volunteers were matched for age, gender and body mass index.ResultsD-dimers (median 0.38 versus 0.19 mg/l, mean 1.12 ± 2.38 versus 0.28 ± 0.3 mg/l; P = 0.003) and sP-selectin (median 204.1 versus 112.4 ng/ml, mean 209.9 ± 124 versus 124.1 ± 32; P = 0.0005) plasma levels were significantly increased in the group of patients with acute psychosis as compared with healthy volunteers. We found a trend (median 148% versus 110%, mean 160 ± 72.5 versus 123 ± 62.5; P = 0.062) of increased plasma levels of factor VIII in psychotic patients as compared with healthy volunteers.ConclusionsThe results suggest that at least a part of venous thromboembolic events in patients with acute psychosis may be induced by pathogenic mechanisms related to psychosis rather than by antipsychotic treatment. Finding an exact cause for venous thromboembolism in psychotic patients is necessary for its effective treatment and prevention.

Cytokines and adhesion molecules in the course of acute myocardial infarction

The plasma levels of interleukin 1 beta (IL 1beta), interleukin 6 (IL 6), interleukin 8 (IL 8), tumor necrosis factor alpha (TNF-alpha), E-selectin, ICAM 1 and C-reactive protein (CRP) have been studied in 24 patients with acute myocardial infarction in the course of 96 h. The plasma IL 1beta and IL 6 levels were continually elevated during the 96 h study period (the peak of plasma IL 1beta level was 22.2 pg/ml, S.D. 8.6, P < 0.001, normal values of IL 1beta are less than 10 pg/ml, the mean peak plasma concentration of IL 6 was 184.9 pg/ml, S.D. 134.7, vs. normal values of 15.57 pg/ml, S.D. 2.4, P < 0.001). The mean plasma IL 8 level was increased for the duration of the study, the mean plasma IL 8 level was 103.0 pg/ml, S.D. 23.4 (normal value was below 30 pg/l, S.D. 8.0) P < 0.001. The plasma TNF-alpha level was elevated throughout the time of observation without any significant peak. The mean plasma TNF-alpha concentration was 46.8 pg/ml, S.D. 2.13, vs. normal value 4.35 pg/ml, S.D. 1.23, P < 0.001. The plasma E-selectin level reached the mean level of 145.1 ng/ml, S.D. 75.4, vs. normal value 29.1-63.4 ng/ml, P < 0.001 at an interval of 15-42 h after the onset of the symptoms. The plasma ICAM 1 level showed only a slight significant increase during the first 36 h. The plasma CRP concentration increased later than IL 6, and reached a peak at 42 h after the onset of the symptoms (69.2 mg/l, S.D. 29.9, vs. 1.2 mg/l, S.D. 4.7, P < 0.0001). We conclude that cytokines and adhesion molecules can play an important role in the mechanisms of tissue injury in the process of ischemia and reperfusion.

CD200/CD200R Paired Potent Inhibitory Molecules Regulating Immune and Inflammatory Responses; part I: CD200/CD200R Structure, Activation, and Function

CD200/CD200R are highly conserved type I paired membrane glycoproteins that belong to the Ig superfamily containing a two immunoglobulin-like domain (V, C). CD200 is broadly distributed in a variety of cell types, whereas CD200R is primarily expressed in myeloid and lymphoid cells. They fulfill multiple functions in regulating inflammation. The interaction between CD200/CD200R results in activation of the intracellular inhibitory pathway with RasGAP recruitment and thus contributes to effector cell inhibition. It was confirmed that the CD200R activation stimulates the differentiation ofT cells to the Treg subset, upregulates indoleamine 2,3-dioxygenase activity, modulates cytokine environment from a Thl to a Th2 pattern, and facilitates an antiinflammatory IL-10 and TGF-beta synthesis. CD200/CD200R are required for maintaining self-tolerance. Many studies have demonstrated the importance of CD200 in controlling autoimmunity, inflammation, the development and spread of cancer, hypersensitivity, and spontaneous fetal loss.

Anti-NMDA receptor antibodies in patients with a first episode of schizophrenia

Background Encephalitis with antibodies against N-methyl-D-aspartate receptor (NMDA-R) is classified as an autoimmune disorder with psychotic symptoms, which are frequently dominant. However, it remains unclear how frequently NMDA-R antibodies lead to a condition that mimics psychosis and first-episode schizophrenia. In our work, we investigated the presence of antibodies against NMDA-R in patients with first-episode psychosis (FEP) in comparison with healthy volunteers. Methods This study included 50 antipsychotic-naïve patients with FEP (including 21 women) and 50 healthy volunteers (including 21 women). The mean age of the patients was 27.4 (±7.4) years and that of the healthy controls was 27.0 (±7.3) years. Antibodies against NMDA-R in the serum were detected by immunofluorescence. Results None of the investigated patients with an FEP and none of the healthy controls showed positive antibodies against NMDA-Rs. Conclusion According to results of studies, a small proportion of patients with an FEP possess antibodies against NMDA-R. However, the extent to which this finding contributes to the etiopathogenesis of the response to antipsychotic medication and whether immunomodulatory therapy is indicated in these cases remains uncertain.

PLASMA INTERLEUKIN-6 LEVEL IS ASSOCIATED WITH NT-PROBNP LEVEL AND PREDICTS SHORT- AND LONG TERM MORTALITY IN PATIENTS WITH ACUTE HEART FAILURE

OBJECTIVES Interleukin 6 plays an important role in chronic heart failure (HF), but little is known about its involvement in acute decompensated heart failure (ADHF). The aim of our study is to evaluate the prognostic role of interleukin 6 (IL-6) in the patients with ADHF. METHODS Plasma levels of interleukin IL-6, N-terminal pro brain natriuretic peptide levels, and clinical covariates were measured in 92 patients with ADHF. Survival was followed up to 12 months, and prognostic factors were evaluated. RESULTS Elevated plasma IL-6 levels were increased in nonsurvivors and were associated with 1-year mortality (p < 0.01). Plasma IL-6 levels were associated with plasma NT-proBNP levels. In multivariate analysis, increased plasma IL-6 and NT-proBNP levels remained strong independent predictors of 1-year mortality. CONCLUSIONS Plasma IL-6 levels provide important prognostic information in the patients with ADHF. Measurement combining plasma IL-6 and NT-proBNP should serve as a powerful prognostic tool of multimarker strategy in patients with acute decompensated heart failure.

CC and CXC chemokines patterns in psoriasis determined by protein array method were influenced by Goeckerman's therapy.

Goeckermans therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. The aim of this study was to evaluate the influence of Goeckermans therapy of psoriasis on the levels of proangiogenic chemokines ENA-78 (CXCL5, Epithelial Cell Derived Neutrophil Attractant-78), GRO alpha (CXCL1, Growth-Related Oncogene), IL-8 (CXCL8, Interleukin-8), MCP-1 (CCL2, Monocyte Chemotactic (Chemoattractant) Protein 1) and RANTES (CCL5, Regulated on Activation of Normal T Cell Expressed and Secreted) in peripheral blood of 22 childrens patients with psoriasis. 22 otherwise healthy children serve as a control group. The serum levels of chemokines were determined by commercial membrane protein array technique (RayBiotech, USA). Efficacy of Goeckermans therapy was delineated by PASI score. Disease activity was significantly diminished by Goeckermans therapy (p < 0.001). Serum levels of GRO alpha and MCP-1 in patients before GT were significantly higher than those measured in healthy blood donors (GRO alpha: p = 0.0128 and MCP-1: p = 0.0003). Serum levels of GRO alpha, MCP-1 and RANTES were significantly diminished by GT (GRO alpha: p = 0.002, MCP-1: p = 0.048 and RANTES: p = 0.0131). Compared to the healthy controls, serum level of MCP-1 remained significantly increased in psoriasis patients after GT (p < 0.0001). In conclusion, we found that the GT of psoriasis influenced the serum levels of proinflammatory and proangiogenic chemokines, especially GRO alpha, MCP-1 and RANTES. It could be the cause for decreased proangiogenic activity which is described after GT of psoriasis.

CD200/CD200R Paired Potent Inhibitory Molecules Regulating Immune and Inflammatory Responses; Part II : CD 200/CD200R Potential Clinical Applications

SUMMARY CD200 and its receptor were recognized as having the multiple immunoregulatory functions. Their immunoregulatory, suppressive, and tolerogenic potentials could be very effectively exploited in the treatment of many diseases, e.g. Alzheimer disease, rheumatoid arthritis, and allergy to name only some. Many research projects are aimed to develop clinically valuable methods being based on the structure and function of these paired molecules. In this review, we would like to introduce CD200/CD200R functions in a clinical context.

Circulating fetuin-A predicts early mortality in chronic hemodialysis patients

OBJECTIVES The purpose of this study was to assess whether low serum levels of fetuin-A are potential biochemical predictor of early and/or late survival in chronic hemodialysis (HD) patients. DESIGN AND METHODS We measured serum levels of fetuin-A in 67 patients on chronic HD, and correlated it to 3, 12, and 24 months mortality. RESULTS Cumulative death rate was 7%, 19%, and 37% deaths at 3, 12, and 24 months. Serum fetuin-A was significantly lower in 3 months and 12 months non-survivals (p<0.001), but not in 24 months non-survivals. Kaplan-Meier analyses based on fetuin-A tertiles showed statistically significantly increased probability of death up to 12 months of follow-up for decreasing fetuin-A concentrations (p<0.008). CONCLUSIONS Fetuin-A as a circulating inhibitor of vascular calcification was significant predictor of early mortality in chronic HD patients but did not appear as a fair marker for later survival.

THE VEGF AND BMP-2 LEVELS IN PATIENTS WITH ANKYLOSING SPONDYLITIS AND THE RELATIONSHIP TO TREATMENT WITH TUMOUR NECROSIS FACTOR ALPHA INHIBITORS

INTRODUCTION Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by the development of osteoproductive changes in the spine which could possibly result in ankylosis. Treatment with tumour necrosis factor alpha (TNFα) inhibitors has proved to be an important step forward in the treatment of this disease, but for the time being it is not clear whether it favourably influences radiographic progression of the disease. Vascular endothelial growth factor most probably plays a role in the development of osteoproductive changes and recently its predictive influence on radiographic progression has been demonstrated. Bone morphogenic protein 2 (BMP-2) participates in the regulation of bone proliferation and its increased serum level has been demonstrated in patients with advanced AS and correlated with the degree of radiographic changes. AIM The study aims to evaluate the VEGF and BMP-2 levels in patients with ankylosing spondylitis and how these levels relate to the concurrent treatment with TNFα inhibitors. METHODS Sera were evaluated from patients at the Rheumatologic Clinic of the Hradec Králové Faculty Hospital who fulfilled the modified New York Criteria for AS (n = 55). In these patients, the parameters of the activity of the disease (BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein) and the concurrent therapy (TNFα inhibitors, n = 21, vs. non-anti TNFα, n = 34) were recorded. The levels of VEGF and BMP-2 were analyzed using the ELISA method. RESULTS In patients treated with TNFα inhibitors, a significantly lower VEGF level was found when compared to untreated patients (140.3 (109.4; 262.2) vs. 261 (172.4; 396.6) pg/ml; p = 0.02). No difference was found between BMP-2 levels in both groups (treated vs. untreated patients) (254.8 (2301; 267.3) vs. 261.1 (248.6; 273.5) pg/ml; p = 0.24). A correlation analysis did not reveal any relationship between VEG F and BMP-2 (r = 0.057; p = 0.68). Serum levels of VEGF correlated with serum levels of CRP (r = 0.56; p = 0.00001) and the BASDAI value (r = 0.33; p = 0.015). CONCLUSION Significantly lower VEGF levels were found in patients treated with TNFα inhibitors versus the untreated patients. These findings are in harmony with some hitherto published analyses and may give evidence of a favourable effect of TNFα inhibitors on radiographic progression. Neither influence on the BMP-2 level by treatment with TNFα inhibitors nor correlation with VEGF levels was demonstrated.

Anti-inflammatory Properties of High-density Lipoprotein Cholesterol in Chronic Hemodialysis Patients: Impact of Intervention

OBJECTIVE Levels of high-density lipoprotein (HDL) cholesterol as well as its functional roles are suppressed in chronic kidney disease because of ongoing chronic microinflammatory state. We hypothesized that intervention aimed at reducing inflammation may improve the levels and activity of HDL cholesterol as well as survival of our patients. METHODS In this prospective follow-up study, we selected 67 patients (33 women, 34 men) on chronic hemodialysis (23.5 months [range, 10 to 34], aged 67.5 years [range, 39 to 90 years]). Targeted examination for asymptomatic infective foci or poor function of arterio-venous (AV)-fistula was carried out after a detailed initial clinical examination in all patients. Individual intervention was performed according to examination results. Blood was drawn for analysis of HDL cholesterol; interleukin-6, its soluble receptor, monocyte chemoattractant protein 1 (MCP-1), total iron binding capacity, and high sensitivity C-reactive protein at the beginning of the study and after 3 months. The patients were then closely followed up for 2 years during which the occurrence and cause of death was registered. RESULTS A significant decrease of inflammatory parameters (Interleukin-6: 4.9 vs. 1.1 pg/mL, P > .001 and MCP-1: 397 vs. 310 pg/mL, P = .02) and increase of HDL cholesterol (1.22 ± 0.55 vs. 1.33 ± 0.55; P = .003) was seen in the entire study population. No difference in survival was found between the different interventional groups. The 2-year death rate was 37%. On using Kaplan-Meier analysis, a significantly better survival in patients with increase of HDL cholesterol (77% vs. 50%; P = .013) and/or a decrease of MCP-1 (81% vs. 53%; P = .04) was found after 3 months of intervention. CONCLUSIONS It was concluded that individually aimed intervention may improve levels of HDL cholesterol and MCP-1. Changes in these 2 parameters can predict the 2-year survival rates of patients.