Relationship between TRAIL and Left Ventricular Ejection Fraction in Patients with ST-Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention

Background. Apoptosis plays an important role in the myocardial injury after acute myocardial infarction and in the subsequent development of heart failure. Aim. To clarify serum kinetics of apoptotic markers TRAIL and sFas and their relation to left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Methods. In 101 patients with STEMI treated with pPCI, levels of TRAIL and sFas were measured in series of serum samples obtained during hospitalization and one month after STEMI. LVEF was assessed at admission and at one month. Major adverse cardiovascular events (MACE, i.e., death, re-MI, and hospitalization for heart failure and stroke) were analysed during a two-year followup. Results. Serum level of TRAIL significantly decreased one day after pPCI (50.5pg/mL) compared to admission (56.7pg/mL), subsequently increased on day 2 after pPCI (58.8pg/mL), and reached its highest level at one month (70.3pg/mL). TRAIL levels on days 1 and 2 showed a significant inverse correlation with troponin and a significant positive correlation with LVEF at baseline. Moreover, TRAIL correlated significantly with LVEF one month after STEMI (day 1: r=0.402, p<0.001; day 2: r=0.542, p<0.001). On the contrary, sFas level was significantly lowest at admission (5073pg/mL), increased one day after pPCI (6370pg/mL), and decreased on day 2 (5548pg/mL). Significantly highest sFas level was marked at one month (7024pg/mL). sFas failed to correlate with LVEF at baseline or at one month. Both TRAIL and sFas showed no ability to predict improvement of LVEF one month after STEMI or a 2-year MACE (represented by 3.29%). Conclusion. In STEMI treated with pPCI, TRAIL reaches its lowest serum concentration after reperfusion. Low TRAIL level is associated with worse LVEF in the acute phase of STEMI as well as one month after STEMI. Higher TRAIL level appears to be beneficial and thus TRAIL seems to represent a protective mediator of post-AMI injury.

Clinical significance of soluble Fas plasma levels in patients with sepsis

Background/Aim. The goal of modern clinical and experimental researches in the field of sepsis is to find one or more sensitive parameters that could predict the severity of sepsis and its outcome. In this study we investigated and compared the relationship of initial soluble Fas (sFas) plasma levels as well as Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) score in 58 septic patients with severity and outcome of sepsis. Methods. The diagnosis and assessment of disease severity was performed on the same day, based on clinical and laboratory parameters. The blood samples were used for monitoring of laboratory standard parameters necessary for the diagnosis of sepsis, organ dysfunction and assessment of disease severity, as well as for determination of levels of sFas. According to consensus criteria, patients were divided into those with sepsis (n = 16), severe sepsis (n = 30) or septic shock (n = 12), those with (n = 26) and without (n = 32) multiple organ dysfunction syndrome (MODS), and survivors (n = 45) and non-survivors (n = 13). Results. Plasma sFas level (9.7 ? 10.1; 0-44.2 U/mL) was elevated in 54.4% of patients. All the patients with septic shock, 76.9% of the patients with MODS and 84.6% patients who died had elevated sFas level. We observed a strong positive correlation between sFas and APACHE II score (p < 0.001). The level of sFas was significantly higher in patients with septic shock compared to normotensive patients (p < 0.001), patients with MODS compared to those without MODS (p < 0.001) and survivors compared to nonsurvivors (p < 0.01). Conclusions. Our results suggest that initial sFas plasma levels in patients with sepsis correlated with the values of APACHE II score and separated very well the patients with septic shock versus the normotensive patients, the patients with and without MODS, and survivors versus non-survivors.

Soluble Fas and the −670 Polymorphism of Fas in Lupus Nephritis

This study was performed to clarify the role of soluble Fas (sFas) in lupus nephritis (LN) and establish a potential relationship between LN and the −670 polymorphism of Fas in 67 patients with systemic lupus erythematosus (SLE), including a subset of 24 LN patients with proteinuria. Additionally, a group of 54 healthy subjects (HS) was included. The allelic frequency of the −670 polymorphism of Fas was determined using PCR-RFLP analysis, and sFas levels were assessed by ELISA. Additionally, the WT-1 protein level in urine was measured. The Fas receptor was determined in biopsies by immunohistochemistry (IHC) andin situhybridization (FISH) and apoptotic features by TUNEL.Results. The −670 Fas polymorphism showed that the G allele was associated with increased SLE susceptibility, with an odds ratio (OR) of 1.86. The sFas was significantly higher in LN patients with the G/G genotype, and this subgroup exhibited correlations between the sFas level and proteinuria and increased urinary WT-1 levels. LN group shows increased expression of Fas and apoptotic features. In conclusion, our results indicate that the G allele of the −670 polymorphism of Fas is associated with genetic susceptibility in SLE patients with elevated levels of sFas in LN with proteinuria.

Second Report of Clinical Significance of sFas for DLBCL Treated with CHOP and New Analysis of sFas for DLBCL Treated with R-CHOP.

Introduction: We have previously reported serum concentration of sFas predict a clinical outcome of patients with DLBCL. Here, we added the number of patients and confirmed that a high serum sFas level was associated with unfavorable prognosis of patients with DLBCL. Patients and methods: We used a prospective, consecutive entry design, and the study protocol was approved by the Institution’s Review Board. Between October 1995 and September 2002 previously untreated 132 patients with DLBCL (Group A: patients treated without rituximab) and between December 2002 and March 2007 previously untreated 75 patients with DLBCL (Group B: patients treated with rituximab) confirmed by biopsy participated in this study. We considered eligible for this study all patients with histologically confirmed diagnosis of DLBCL, according to the Working-Formulation and the WHO classification. Serum sFas was determined using ELISA. Patients were assigned to receive eight cycles of CHOP or THP (tetrahydropyranyl-adriamycin) -COP therapy before September 2002. The patients who had been registered after October, 2002 received the R-CHOP or R-THP-COP therapy. A serum sFas level of 3.0ng /ml was used as the cut-off value in this study. All follow-up data were updated on March 1, 2007. Results: In Group A: 132 patients were enrolled in this category (82 males, 50 females, age; 14 to 92 years, median; 66 years). IPI scoring was available in all patients; accordingly 18.2% patients were classified as low risk, 25.8% as low-intermediate; 32.6% as high-intermediate, and 23.5% as high risk. Overall, the CR rate was 73.5%; PRs were observed in 7.6% and failures in 18.9%. The CR rates for patients with an sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 51.1% and 81.6%, respectively (P&lt;0.0005). The 5-year OS rates for patients with an sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 19.8% and 61.9%, respectively (P&lt;0.0001). In Group B: 75 patients were enrolled in this category (42 males, 33 females, age; 24 to 88 years, median; 69 years). IPI scoring was as follows; 22.6% patients were classified as low risk, 26.6% as low-intermediate; 21.3% as high-intermediate, and 29.3% as high risk. Overall, the CR rate was 72.0%; PRs were observed in 22.7% and failures in 5.3%. The CR rates for patients with a sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 65.6% and 76.7%, respectively (NS). The 2-year OS rates for patients with an sFas level of 3.0ng /ml and over and less than 3.0ng /ml were 54.7% and 92.2, respectively (P&lt;0.01). Multivariate analysis using the proportional hazards model revealed that sFas concentration significantly correlated with overall survival in both group A and B (p&lt;0.05). Discussion: The IPI is now considered as the most reliable index. After introduction of rituximab to treat for B cell lymphoma, the change of the prognostic factor is expected. In this examination, initially, we could confirm that sFas was an important prognostic factor for DLBCL in the patients who are treated with CHOP regimen as a result of extending the period of surveillance. In addition, we could show that sFas is a useful prognostic factor for DLBCL in the patients who are treated with R-CHOP regimen, too. Conclusion: Serum sFas is a significant prognostic factor for DLBCL and a useful tool for selecting the appropriate therapeutic strategy in patients with DLBCL.

Increased apoptosis of peripheral blood mononuclear cells in patients with perennial allergic asthma/rhinitis: relation to serum markers of apoptosis

Background: The goal of our study was to examine spontaneous and stimulated apoptosis of peripheral blood MNC from allergic patients, sensitized to Der p I antigen as compared to cells from non-atopic subjects. Furthermore we aimed to investigate which populations of mononuclear cells (lymphocytes, monocytes) undergo the apoptosis and to determine relations between apoptosis and serum levels of sFas/APO-1, ICE/caspase-1 or TNF-α.Methods: The study included 17 patients with perennial, allergic asthma and/or allergic rhinitis [6 male and 11 female; mean age 29,5 years; (range 15-49)].Apoptosis was assessed by fluorescence technique and confirmed by flow-cytometric method and DNA ladder. Serum levels of sFas, ICE/caspase-1 or TNF-α were determined by immunoassays (ELISA).Results: Apoptotic index of unfractionated mononuclear cells (MNC) and lymphocytes (but not monocytes) were significantly higher in allergic patients as compared to non-allergic subjects after 48 and 72 hours of culture (p<0.05). Incubation of cells with ConA (10 μg/ml) resulted in a significant increase in the proportion of apoptotic cells in all populations once the apoptotic index for MNC and lymphocytes (but not monocytes) was again significantly higher in allergic as compared to non-allergic subjects after 24, 48 and 72 hour of culture.In allergic patients, mean serum sFas level, was significantly lower then in non-allergic group (mean value 624.8 pg/ml ± 25.67 versus 802.0 pg/ml ± 31.91;p=0.003) and in both groups sFas level correlated inversely with apoptosis of MNC. The mean ICE/caspase-1 concentration was significantly higher in sera of allergic patients as compared to non-allergic group (mean value 27.71 pg/ml ± 3.79 vs 23.54 pg/ml respectively;p<0.01). ICE/caspase-1 levels in allergic patients correlated with apoptotic index of mononuclear cells (r=0.57;p<0.001).Conclusions: An increased spontaneous and mitogen-induced apoptosis of MNC from peripheral blood of atopic patients as well as different serum levels of sFas and ICE/caspase-1 correlating with apoptosis, suggest different regulation of apoptotic process in peripheral blood mononuclear cells of patients with allergic asthma and/or rhinitis.