Violetta Dymicka-Piekarska

Does Toxoplasma gondii Infection Affect the Levels of IgE and Cytokines (IL-5, IL-6, IL-10, IL-12, and TNF-alpha)?

In the study performed in a group of patients infected with T. gondii, we evaluated Th2 humoral response (IL-5, IL-6, IL-10) and Th1 cell response (IL-12, TNF-α). The study objective was to assess the effect of T. gondii on chosen indices of the immune response. The study involved 52 women infected with T. gondii (aged 18–42 years) prior to antiparasitic treatment. In all the patients, we found IgM (index >0.7) and IgG which exceeded 300 IU/ml. The control group (C) consisted of 40 healthy women aged 18–46 years. In the study group (T) and in the control group (C), the levels of IgE, IL-5, IL-6, IL-10, IL-12, and TNF-α were determined. In our study, T. gondii patients had twofold higher levels of IL-5 and IL-6 as compared to healthy subjects, which seems to confirm the presence of an inflammatory state. We found the level of IL-10 to be fivefold higher in the course of toxoplasmosis than in healthy controls. The levels of IL-12 and TNF-α were comparable to those observed in healthy controls. The study has revealed that patients infected with T. gondii show increased production of the humoral response cytokines, whereas the generation of the cell response cytokines remains unchanged.

IFN-gamma, IL-5, IL-6 and IgE in patients infected with Giardia intestinalis.

The immune system, its cellular and humoral response, is engaged by the host organism to fight against parasitic infections. The study group consisted of 90 patients (58 women and 32 men), aged 18-72 years, infected with G. intestinalis. The diagnosis was established based on laboratory investigations (stool examination, choloscopy, GSA-65). Blood for analysis was collected before (G1), and 2 weeks (G2) and 2 months (G3) after antiparasitic treatment. Control group consisted of 40 healthy subjects (22 women and 18 men), aged 20-45 years. The concentrations of IgE were assayed using a set of VIDAS (bioMerieux) and the concentrations of IL-5, IL-6, IFN-gamma were determined using a set of Quantikine human (R&D Systems). It was revealed that in giardiosis the concentrations of IgE and IL-5 in blood serum were twice as high, the concentration of IL-6 was two and a half times higher and the concentration of IFN-gamma was almost four times higher as compared to healthy controls.

Does colorectal cancer clinical advancement affect adhesion molecules (sP- selectin, sE- selectin and ICAM-1) concentration?

Adhesion molecules take part in physiological and pathological processes. They involved in inflammatory reactions and play important role in tumor invasion and the development of metastases. Soluble forms of P-selectin, E-selectin and ICAM-1 have been described in this study in patient with colorectal cancer. Plasma was obtained from 44 patients with colorectal cancer and 34 control subjects prior surgery, by an enzyme-linked immunosorbent assay (ELISA). The patients were divided according to TNM classification. Plasma level of all three molecules was significantly higher in colorectal cancer patients than in the control (p < 0.001). The highest level of sE-selectin and ICAM-1 were observed in patients with liver metastasis. There was no correlation between sP-selectin and sE-selectin, but we found a significant correlation between sE-selectin and ICAM-1 in all patients. These findings suggest that plasma concentration of E-selectin and ICAM-1 may indicate tumor progression and liver metastasis.

Prognostic significance of adhesion molecules (sICAM-1, sVCAM-1) and VEGF in colorectal cancer patients.

INTRODUCTION Adhesion molecules take part in the interaction between host cells and cancer cells. In the current study the relationship between the soluble adhesion molecules sICAM-1 and sVCAM-1 and proangiogenic factor VEGF in colorectal cancer progression were measured. MATERIALS AND METHODS The study group consisted of 46 patients with colorectal carcinoma (classified due to TNM classification) and 40 controls. sICAM-1, sVCAM-1 and VEGF plasma concentration were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS All measured parameters levels were increased significantly in patients with colorectal cancer in comparison to controls (p<0.001). sICAM-1, sVCAM-1 and VEGF increased significantly due to colorectal cancer progression. There was a positive correlation between sICAM-1 and sVCAM-1 in all study groups. CONCLUSIONS Our results demonstrated in CRC patients significantly increased levels of soluble adhesion molecules (VCAM-1 and sICAM-1) and angiogenic factor (VEGF) as compared to control group. The dynamics of these molecules showed the growing tendency along with tumor size and metastasis formation.

Multifunctional CD40L: pro- and anti-neoplastic activity.

The CD40 ligand is a type I transmembrane protein that belongs to a tumor necrosis factor (TNF) superfamily. It is present not only on the surface of activated CD4+ T cells, B cells, blood platelets, monocytes, and natural killer (NK) cells but also on cancer cells. The receptor for ligand is constitutively expressed on cells, TNF family protein: CD40. The role of the CD40/CD40L pathway in the induction of body immunity, in inflammation, or in hemostasis has been well documented, whereas its involvement in neoplastic disease is still under investigation. CD40L ligand may potentiate apoptosis of tumor cells by activation of nuclear factor-κB (NF-κB), AP-1, CD95, or caspase-depended pathways and stimulate host immunity to defend against cancer. Although CD40L has a major contribution to anti-cancer activity, many reports point at its ambivalent nature. CD40L enhance release of strongly pro-angiogenic factor, vascular endothelial growth factor (VEGF), and activator of coagulation, TF, the level of which is correlated with tumor metastasis. CD40L involvement in the inhibition of tumor progression has led to the emergence of not only therapy using recombinant forms of the ligand and vaccines in the treatment of cancer but also therapy consisting of inhibiting platelets-main source of CD40L. This article is a review of studies on the ambivalent role of CD40L in neoplastic diseases.

Predictive value of Galectin-3 for the occurrence of coronary artery disease and prognosis after myocardial infarction and its association with carotid IMT values in these patients: A mid-term prospective cohort study

OBJECTIVE The role of Galectin-3(Gal-3) in atherosclerosis progression has not been definitely acknowledged. The aim of the study was to establish the following: whether Gal-3 may act as an independent risk factor of coronary artery disease (CAD) occurrence and its advancement, if Gal-3 has potential relations with classical and new markers of cardiovascular risk (carotid intima-media thickness (cIMT), and whether Gal-3 may be a marker of mortality in the group of patients with myocardial infarction (MI) during mid-term follow-up. PATIENTS AND METHODS The study group was composed of 233 patients with MI and 100 patients with a stable CAD. Selected risk factors were assessed, Gal-3 concentrations and cIMT were measured. The control group was composed of 100 healthy individuals. RESULTS In the study group (MI and CAD patients) Gal-3 concentration was significantly higher than in the controls--median 7.9 ng/ml (p = 0.0001) and 10.7 ng/ml (p = 0.00001) vs. 5.5 ng/ml, respectively. Patients with 3-vessel disease had higher levels of Gal-3 than patients with 1-or 2-vessel disease (9.2 ng/ml vs 7.4 ng/ml, p = 0.003). In the group of MI patients who died during the follow-up (average period - 2.8 years), we found a significantly higher concentration of Gal-3 (20.0 ng/ml vs 8.0 ng/ml, p = 0.0005) and cIMT values (common carotid artery(CCA): 1.4 ± 0.4 mm vs. 1.0 ± 0.3 mm, p = 0.03; carotid bulb(CB): 2.3 ± 0.5 mm vs. 1.9 ± 0.4 mm, p = 0.009). In the model of multivariate logistic regression analysis, the variables influencing the mortality after MI during follow-up were: age>65 years, Gal-3 concentration>8.7 ng/ml, IMT values and plaque occurrence in CB, previous MI and EF<40%. CONCLUSIONS Gal-3 is an independent risk factor of CAD occurrence, but cIMT values are better markers of CAD advancement. Both Gal-3 concentration>8.7 ng/ml and IMT values in CB were an independent predictive indicators of increased risk of all-cause mortality in patients after MI during mid-term follow up.

Activation of blood platelets in echinococcosis — CD62P and CD63 expression

The immune system is involved in the fight against parasitic invasions on the pathway of cellular and humoral responses. Th1 lymphocytes, through the released cytokines [interleukin-2 (IL-2), interferon gamma (IFN-γ), and interleukin-12 (IL-12)], induce differentiation and proliferation of cytotoxic cells and activate macrophages by intensifying their ability to kill parasites (Ishikawa et al. 1998). The antibody-dependent antiparasitic immunity displays a few mechanisms that cause blocking of the parasite surface receptor, induce direct damage of the parasite through complement activation or increase immunoglobulin E (IgE) production (Bulut et al. 2001; Ferreira et al. 2000; Polack et al. 1991; Souza-Atta et al. 1999). Platelets participate in various stages of blood clotting, in sclerosis, coronary disease, neoplasms, inflammatory processes, and in allergic and immune reactions (Baj 1997; Klinger and Jelkmann 2002; Mannaioni et al. 1997). A number of factors, including thrombin, adenosine diphosphate (ADP), and serotonin, activate platelets in all these conditions. Platelet activation is also induced by enhanced clotting forces affecting blood corpuscles at the sites of vessel narrowing and laminar blood flow disorders (Clemetson 1995). Parasitic invasions are the source of foreign antigens and exotoxins which trigger local or systemic inflammatory processes. Antibody-dependent cellular toxicity is the major antiparasitic defensive mechanism, with eosinophils as the effector cells. Macrophages, neutrophils, and platelets develop cytotoxic activity against antibody-coated parasites (Polack et al. 1991; Souza-Atta et al. 1999). Blood platelets initiate and maintain inflammatory processes through secretion of the platelet activating factor (PAF), platelet-derived growth factor (PDGF), human platelet factor 4 (PF4), β-thromboglobulin, IL-1 and leukotrienes. Platelets are activated by their contact with immunocompetent cells or directly with a parasite, in the presence of IgE, IgG, lymphokines, or complement components. The activated platelet changes its morphological parameters, thus, their measurement can be indirectly indicative of activation (Blockmans et al. 1995). Patients infected with Echinococcus granulosus were subjected to examinations evaluating activation of blood platelets and their reactivity by determining the expression of platelet receptors CD62P and CD63. The study aimed to find out whether infection with E. granulosus affects the above-mentioned parameters.

Plasma C16-Cer levels are increased in patients with preterm labor.

INTRODUCTION The pathogenesis of preterm labor is fragmentarily explained. The most widely accepted theory points out to infection and inflammation as possible causes, which can be mediated by potentially different factors, including sphingolipid mediators. Sphingolipids are a class of lipids that have been shown as important mediators in various cell processes such as: proliferation, growth, apoptosis, stress response, necrosis and inflammation. The aim of the study was to assess plasma concentrations of selected sphingolipids in patients with preterm labor. MATERIAL AND METHODS We used ultra-high performance liquid chromatography with triple mass spectrometry (UHPLC-ESI-MS/MS) to assess plasma concentrations of the 11 sphingolipids in patients presenting with symptoms of preterm labor (n=61) and threatened preterm labor (n=40). RESULTS We observed a statistically significant increase (p-value<0.004) in plasma concentrations of C16-Cer in patients with preterm labor as compared to the control group. We also found C16-Cer to be the best predictor of preterm labor in the group of patients with symptoms occurring after 32 weeks of gestation. CONCLUSIONS Our findings show a possible involvement of selected sphingolipids, especially C16-Cer, in the pathogenesis of preterm labor. Their role as predictors of preterm delivery needs to be validated in the future on larger group of patients.

Application of the Bead-Based Technique in Neurodegeneration: A Literature Review.

Background: Alzheimers disease (AD) is the most common disease causing neurodegeneration. The lower concentration of β-amyloid 1-42 (Aβ1-42) together with increased levels of total tau protein (T-tau) and phosphorylated tau protein (P-tau) in the cerebrospinal fluid (CSF) make a panel of well-established biomarkers in AD diagnosis. Addition of novel biomarkers to the gold standard biomarker panel might improve the diagnostic accuracy of neurodegeneration. This goal might be reached by the use of multiplexing, which is a simultaneous measurement of multiple analytes in a single sample volume and within a single cycle or run. Objective/Methods: Therefore the aim of the current review was to present, according to our best knowledge, available data concerning the evaluation of concentrations and diagnostic accuracy of well-established biomarkers in AD as well as novel biomarkers analyzed with the use of the bead-based technique. Additionally we discuss the utilization of the bead-based technique as compared to the conventional ELISA method. Results: Literature data indicate that the bead-based technique revealed diagnostic sensitivity, specificity and coefficients of variation at the levels similar to ELISA. Moreover, an addition of novel biomarkers (tested by means of the bead-based technique) to the gold standard biomarker panel improved the diagnostic accuracy of neurodegeneration. Conclusion: Review of literature data shows that the combined analysis of classical CSF biomarkers with novel biomarkers might increase the specificity and sensitivity of performed tests. However, we concluded that the replacement of conventional ELISA with the bead-based technique requires new reference intervals for Aβ1-42, T-tau and P-tau concentrations.

sVCAM-1 concentration and carotid IMT values in patients with acute myocardial infarction – Atherosclerotic markers of the presence, progress and prognosis

PURPOSE Vascular cell adhesion molecule 1 (VCAM-1) plays a role in the adhesion and migration of leukocytes from blood to arterial intima and correlate with the development of atherosclerosis. The aim of the study was to establish whether soluble VCAM-1 (sVCAM-1) may act as an independent risk factor of coronary artery disease occurrence and whether it may reflect a degree of its advancement, if sVCAM-1 has a potential relation with intima-media thickness measurement (IMT), if sVCAM-1 may be useful as a predictor of further cardiovascular events. MATERIAL AND METHODS The study group was composed of 78 patients who were consecutively hospitalized in 2010-2011 due to myocardial infarction (MI). Selected clinical and biochemical risk factors were assessed, sVCAM-1 concentrations and IMT were measured. RESULTS Concentrations of sVCAM-1 were significantly higher in the study group as compared to the healthy controls. No significant dependence between sVCAM-1 concentration and the value of IMT in carotid arteries was found. There were no significantly statistical differences between the advancement of coronary artery changes and sVCAM-1 concentration. During the follow-up that lasted from 2 to 4 years (average period - 2.8 years), 4 patients died in the study group (5.1%). sVCAM-1 concentrations (but not IMT values) were significantly statistically higher in the group of patients who died (2248.5±443.5 vs. 990.2±433.6, p=0.0003). CONCLUSIONS sVCAM-1 concentrations are useful indicators of the presence of atherosclerosis in coronary arteries, but not its advancement. sVCAM-1 (but not IMT) can be a predictive indicator of an increased risk of death during follow-up in patients after myocardial infarction.