Thrombin-activatable fibrinolysis inhibitor Thr325Ile polymorphism and plasma level in breast cancer: A pilot study.

This study aimed to investigate thrombin-activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphism and TAFI antigen (Ag) levels in breast cancer (BC) in the Egyptian population to clarify their role in relation to BC. A group of 300 females was recruited in this study; of these 150 unrelated patients with different stages of BC and 150 age-matched healthy controls. Plasma TAFI Ag was measured by ELISA and TAFI Thr325Ile (rs1926447) polymorphism was genotyped using TaqMan single nucleotide polymorphism (SNP) genotyping assay. The results showed the genotypes of the minor allele; Thr/Ile (CT) and Ile/Ile (TT) were significantly more frequent in patients compared to control group (50.0% and 22.0% vs. 42.0% and 13.3%, respectively) and were also associated with BC susceptibility [OR = 1.9 and 2.6; 95% CI: (1.1-3.3) and (1.3-5.5), respectively P = 0.01]. Ile325 allele carriers were more frequent in cases than in controls (47.0% vs. 34.0%) [OR = 1.7, (95% CI = 1.2-2.4), P = 0.001]. However, TAFI Thr325Ile polymorphism was not associated with BC stage or other clincopathological characteristics. TAFI Ag levels were correlated with advanced stages of BC, poor prognosis and risk of recurrence (P = 0.02, P = 0.04 and P  < 0.001, respectively) and Thr325Ile SNP was significantly correlated with TAFI antigen levels with the C/C genotype corresponding to the highest and the T/T genotype to the lowest TAFI antigen levels (P < 0.001) in the study groups. In conclusion, this study showed for the first time that TAFI Thr325Ile polymorphism could have a contribution to BC susceptibility in our population. Furthermore, high TAFI plasma levels may serve as a predictor of poor prognosis in patients with BC.

Plasma thrombin-activatable fibrinolysis inhibitor levels and Thr325Ile polymorphism as a risk marker of myocardial infarction in Egyptian patients.

OBJECTIVE: The objective of this study was to investigate whether thrombin activatable fibrinolytic inhibitor (TAFI) Thr325Ile polymorphism and TAFI antigen (Ag) levels could constitute a risk marker of myocardial infarction (MI) in Egyptian patients. STUDY POPULATION AND RESULTS: The study included forty-six patients with acute MI (mean age 55.7 +/- 8.1 years, 33 men, 13 women) compared with age and sex-matched healthy volunteers (n = 54) as a control group. Clinical examination, laboratory investigations, electrocardiography (ECG) and/or echocardiography were done. TAFI Thr325Ile (reference sequence: rs1926447) polymorphism was genotyped in both studied groups using TaqMan SNP (single nucleotide polymorphism) genotyping assay. The genotypes of the high-risk allele [Thr/Ile (CT) and Ile/Ile (TT)] were significantly more frequent in patients compared with the control group (54.4% and 32.6% vs. 51.8% and 5.6%, respectively) and were also associated with an increased risk of MI [OR = 4.95, (95% CI: 1.80 - 13.63); P = 0.0001]. Ile325 allele carriers were more frequent in cases than in control subjects (60.0% vs. 31.5%) [OR = 3.26, (95% CI = 1.82 - 5.83), P = 0.001]. The Thr325Ile SNP significantly correlated with TAFI antigen levels with the C/C genotype corresponding with the highest and the T/T genotype with the lowest TAFI antigen levels (P < 0.001). No statistically significant relation was found between TAFI Thr325Ile polymorphism and either the type or the site of MI. CONCLUSIONS: TAFI Thr325Ile and its respective plasma protein level could have a contribution to MI risk in the Egyptian population.This could be helpful in refining a risk profile for coronary heart disease (CHD) patients.

T helper type 1/T helper type 17-related cytokines in chronic hepatitis C patients before and after interferon and ribavirin therapy.

OBJECTIVE: This study examined the T helper (Th) 1/Th17-related cytokines, interferon (IFN)-γ and interleukin (IL)-17 in the serum of biopsy-proven chronic hepatitis C patients before and after IFN and ribavirin therapy to address whether or not viral clearance is related to Th1/Th17 cytokines. SUBJECTS AND METHODS: The serum levels of IFN-γ and IL-17 were assayed by ELISA on 26 patients with chronic hepatitic C virus (HCV) infection before the start and 3 months after treatment with pegylated IFN-α plus ribavirin and compared with sera from 15 normal control subjects. RESULTS: IFN-γ and IL-17 levels are higher in the serum of patients with chronic hepatitis than in normal controls and these elevated levels were not directly correlated (r = -0.01, p = 0.96 for IFN-γ and r = -0.08, p = 0.66 for IL-17) to the viremic state of the HCV infection. In contrast to IL-17, IFN-γ showed significant reduction after 12 weeks of treatment with pegylated IFN plus ribavirin. However, IFN-γ and IL-17 serum levels were not significantly (p = 0.19 and = 0.70, respectively) different among responders and nonresponders for pegylated IFN plus ribavirin therapy. CONCLUSION: Our findings suggest that the combined treatment with pegylated IFN-α and ribavirin downmodulates the secretion of key cytokine IFN-γ as early as 12 weeks after treatment in infected patients. These findings could encourage new exciting possibilities for immune-based interventions with the aim of restoring functional antiviral T cell responses combined with improved viral clearance.

In vitro assessment of platelet storage lesion in leucoreduced random donor platelet concentrates.

BACKGROUND: Currently platelet concentrates (PC) are collected using different synthetic materials and different centrifugation/leucocyte-removal processes. Upon exposure to artificial surfaces and high centrifugation forces, blood cells can undergo various levels of stress-induced, cellular activation/fragmentation and release reactions which may not only influence the extent of the platelet storage lesion but may also contribute to poor clinical effectiveness of the PC and transfusion reactions. MATERIALS AND METHODS: An array of assays, used for quality control of PC, was performed in two different groups of PC prepared from random donor plasma on days 1, 3 and 5 of storage. The group 1 PC were not leucoreduced while the group 2 PC underwent prestorage leucoreduction using a PL50E filter. As current recommendations for the evaluation of PC include the measurement of platelet activation, in this study CD62P on platelet membrane was measured. Furthermore, in vitro studies indicate that sHLA antigens may modulate immune competent cell function so, the presence of sHLA-1 in blood components is considered a marker of immunological reactivity and this, too, was measured. RESULTS: The levels of CD62P and sHLA-1 were significantly lower in leucoreduced PC than in non-leucoreduced ones. However, the overall rate of increase of sHLA-1 during storage was faster in the leucoreduced group of PC. No significant differences were detected regarding other assays of quality. CONCLUSION: Based on our findings, leucoreduced PC differ from non-leucoreduced ones in terms of some specific markers such as CD62P as a marker of platelet activation and sHLA-1 as a marker of immunological reactivity. Pre-storage leucofiltration, followed by storage in currently used plastic bags is a safe procedure for PC for up to 5 days. The available leucoreduction technologies are not, however, sufficiently robust to completely abrogate transfusions reactions, and improvements are required to reach the goal of optimised yield and minimal transfusion reactions with platelet therapy.

Flow cytometric analysis of the phagocytic cells in active pulmonary tuberculosis.

Phagocyte function in the presence of tuberculosis (TB) assumes increasing importance in Africa, where TB is endemic and bacterial super infection is common. In this study a whole-blood flow cytometric assay was used to analyze the phagocytic capacity of granulocytes and monocytes in patients with active pulmonary tuberculosis. The assay measures the proportion of fluorescence-labelled cells with ingested bacteria and the capacity (fluorescence intensity) of each cell to phagocytose the bacteria. Fifteen patients and 10 healthy controls were assessed. The mean percentage of phagocytosing granulocytes was 82.5% (+/- 16%) in the TB patients, while in the control group it was 97.1% (+/- 2.5 %) (P<0.01). For monocytes, the mean percentage of phagocytozing cells was 57.6% (+/- 26%) in the TB group as compared to 85.8% (+/- 9.3 %) in the control group (P<0.001). On the other hand, granulocytes and monocytes from the TB patients showed significant reduction in the phagocytic capacity as shown by decreased mean florescence intensity (P<0.001). It is concluded that the phagocytic function in active pulmonary TB is impaired possibly contributing to the enhanced susceptibility to opportunistic infections in these patients.