Danijela Jovanovic

Influence of Different β-Blockers on Platelet Aggregation in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy

Introduction: The use of β-blockers in the treatment of patients with coronary heart disease is associated with a decrease in the frequency of angina pectoris and mortality of patients. Due to the severity of the disease and previous cardiovascular interventions, many patients with coronary artery disease (CAD) use dual antiplatelet therapy to achieve greater inhibition of platelet aggregation. The influence of β-blockers on platelet aggregation in patients using antiplatelet therapy is not well understood. Objective: To examine the effect of different β-blockers on platelet aggregation in patients on dual antiplatelet therapy. Methodology: The study included 331 patients who were treated at the Department of Cardiology, Clinical Center Kragujevac during 2011. Patients were divided into 4 groups depending on the type of β-blockers that were used (bisoprolol, nebivolol, metoprolol, and carvedilol). Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test (to assess the effect of clopidogrel), ASPI test (to assess the effect of acetyl salicylic acid), TRAP test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP ASPI/TRAP (ASPI - aranchidonic acid induced aggregation, TRAP - thrombin receptor activating peptide) representing the degree of inhibition of platelet aggregation compared to the basal value. In consideration were taken the representation of demographic, clinical characteristics, laboratory parameters, and cardiovascular medications between the groups. Results: Patients who used nebivolol had a significantly lower value of the ratio of ADP/TRAP (0.39 ± 0.30) compared to patients who used bisoprolol (0.48 ± 0.26; P = .038), and trend toward the lower values of ADP test (328.0 ± 197.3 vs 403.7 ± 213.2; P = .059), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups. Conclusion: Patients with CAD on dual antiplatelet therapy who used nebivolol had significantly lower levels of residual ADP-induced platelet aggregation compared to baseline than patients who used bisoprolol.

Possible role of CD22, CD79b and CD20 expression in distinguishing small lymphocytic lymphoma from chronic lymphocytic leukemia

Aim of the study Flow cytometry has an important role in diagnosis and classification of B-cell lymphoproliferative disorders (BCLPDs). However, in distinguishing chronic lymphocytic leukemia (CLL) from small lymphocytic lymphoma (SLL) only clinical criteria are available so far. Aim of the study was to determine differences in the expression of common B cell markers (CD22, CD79b and CD20) on the malignant lymphocytes in the peripheral blood samples of CLL and SLL patients. Material and methods Peripheral blood samples of 56 CLL and 11 SLL patients were analyzed by 5-color flow cytometry on the CD45/CD19/CD5 gate for CD22, CD79b and CD20. Results In the samples collected from the CLL patients, CD22 expression was detected in only 20% of patients in the low pattern, while in SLL patients the expression was medium and present in 90.9% of patients (p < 0.0001). For CD79b expression, statistical significance is reached both in the expression pattern, which was low/medium for CLL and high for SLL, and expression level (p = 0.006). The expression of CD20 was counted as the CD20/CD19 ratio. The average ratio was 0.512 in the CLL patients vs. 0.931 in the SLL patients (p = 0.0001). Conclusions The pattern of expression and expression level of CD22, CD79b and CD20 in peripheral blood could be used for distinguishing SLL from CLL patients.

Radioiodine therapy accelerates apoptosis in peripheral blood lymphocytes of patients with differentiated thyroid cancer.

Both apoptosis and micronuclei formation reflect cytogenetic damage in cells and could contribute to cell homeostasis. The aim of this study was to evaluate apoptosis in peripheral blood lymphocytes (PBLs) of patients with differentiated thyroid cancer (DTC) before and after 131-iodine (131-I)-therapy and its correlation with micronuclei (MN) frequency. The study population included 18 DTC patients and 18 healthy donors. Apoptotic cells were detected using the Annexin V-FITC/7-AAD kit and MN frequency by cytokinesis-block MN assay. The difference between early apoptosis in PBLs of DTC patients before therapy and controls (9.88 ± 4.99% vs. 6.64 ± 2.07%, p = 0.003) was significant, as well as between early apoptosis in PBLs of DTC patients before and after 131-I-therapy (9.88 ± 4.99% vs. 13.53 ± 6.57%, p = 0.008). The MN frequency and early apoptosis in PBLs of DTC patients was positively correlated before (r = 0.540, p= 0.021) and after 131-I-therapy (r = 0.585, p= 0.014). Thyroid cancer patients had a significantly increased early apoptosis in PBLs, which further increased after 131-I-therapy in association with MN frequency.

Isolated myeloid sarcoma of the neck and chest: differential diagnosis and therapeutic approach

Abstract In this article, we present the case of a 57-yearold man with cervical and mediastinal tumor mass, normal blood count as well as virusological status. Cervical tumor tissue biopsy revealed cells positive for CD34, CD13, LCA, CD33, and CD163 but negative for T-cell and B-cell markers, NK-cell markers, plasmacytic markers and anaplastic large cell lymphoma markers. These features were consistent with myeloid sarcoma of the neck with involvement of the mediastinum. We discussed differential diagnosis and therapy of isolated myeloid sarcoma and suggest that clinical presentation, cell morphology, complete immunophenotype, and specific genotypic lesions in some cases, must be evaluated.

Oxidative Stress Parameters after Abdominal Hysterectomy and their Relationships with Quality of Recovery

Abstract Study aimed to investigate relationship between oxidative stress markers and postoperative recovery in woman after abdominal hysterectomy, as well as to test the hypothesis that different analgesics differently influence redox status. The quality of recovery was evaluated with a QoR-40 questionnaire in fifty-one patients who underwent abdominal hysterectomy, preoperatively and on the 1st, 2nd, 3rd postoperative days (POD1,2,3). Blood samples were collected at baseline (T0), 3 (T1), 24 (T2), 48 (T3) and 72 (T4) hours after surgery. Oxidative stress markers concentrations (TBARS, NO2−, H2O2, O2− ) as well as antioxidative enzymes (SOD, CAT, and GSH) were analyzed. QoR-40 total score significantly declined on POD1 and POD2 and returned to baseline levels on POD3 (p<0.001). H2O2 levels significantly decreased from T0 to T3 and then, increased at T4 (p=0,011). Changes of TBARS and H2O2 from T0 to T3 showed significant and negative correlation (r=−0.303, p=0.046). There was no significant correlation between QoR-40 total score and any parameter of oxidative stress response (p>0.05). Changes in TBARS levels from T0 to T3 were statistically significant between the study subgroups primarily due to increase of the concentrations in patients receiving paracetamol (p=0.031). Patients age, duration of surgery and cigarette smoking status showed significant influcences on and association with some oxidative stress response markers (TBARS, O2−, CAT) (p<0.05). Women who underwent hysterectomy had significant changes of H2O2 and TBARS activity however, those changes were not associated with changes of QoR-40 total scores during recovery.

Cytotoxic, proapoptotic and antioxidative potential of flavonoids isolated from propolis against colon (HCT-116) and breast (MDA-MB-231) cancer cell lines

Isolated and structurally confirmed, eleven flavonoids from propolis were examined for their cytotoxicity toward human colon cancer and human breast cancer cells. Their effect on induction of apoptosis and their antioxidative activities were also evaluated. Six flavonoids induced cytotoxic effects in both cell lines. Luteolin had a marked effect on both cell lines, especially on HCT-116 cells (IC50 72h, 66.86μM). Also, luteolin was observed to have the highest apoptotic potential after 72h treatment of examined cell lines (27.13% and 37.09%, respectively). Myricetin exhibited selective inhibition of cell growth (IC50 114.75μM) and induced apoptosis in MDA-MB-231 cells only. Luteolin and galangin exhibited prooxidative properties 24h after the treatment in HCT-116 cells, while myricetin induced prooxidative effects in MDA-MB-231 cells. On the other hand, selected flavonoids exhibited antioxidative properties 72h after the treatment, decreasing superoxide anion radical and nitrite levels in both cell lines. Cytotoxic and proapoptotic effects on colon and breast cancer cell lines and the influence on their redox status make tested flavonoids good candidates for developing new anticancer drugs.

Extramedullary Involvement of Lymph Nodes in Multiple Myeloma

Abstract Myeloma multiplex is a malignant disease of bone marrow plasma cells. It is usually confined to the bone marrow, but in rare cases, patients can develop extramedullary disease. The involvement of lymph nodes is rare and can be a diagnostic challenge. Here, we describe a 36-year-old male patient who presented with abdominal pain and discomfort initially. An abdominal ultrasound followed by computed tomography (CT) revealed retroperitoneal and mesenteric lymph node enlargement. Biopsies of the abdominal lymph node and infiltrated colon showed a plasma cell infiltrate positive for CD79α, CD38, CD138, kappa light chain and VEGF2. Multiple myeloma with extramedullary localization was diagnosed. After six cycles of chemotherapy consisting of doxorubicin, dexamethasone and thalidomide followed by autologous haematopoietic cell transplantation, the patient achieved complete remission. Specifically, a CT scan after therapy showed enlarged lymph nodes in the abdomen, but PET CT scans did not detect any metabolically active foci. Thee years after the completion of therapy, the patient remains in remission. This case illustrates a rare presentation of extramedullary myeloma involving the abdominal lymph nodes, which could have been potentially mistaken for a lymphoid malignancy.

Blood cells in thyroid cancer patients: a possible influence of apoptosis

Abstract The side effects of radioactive iodine (131-I) treatment of differentiated thyroid cancer (DTC) patients include reduction of peripheral blood cell counts. The aim of this study was to analyze some potential changes in blood cell counts of DTC patients after 131-I therapy, especially CD3-positive, CD19-positive, and CD56-positive peripheral blood lymphocytes (PBL), as well as the possible role of apoptosis in selected lymphocyte populations. The study group included 24 thyroid cancer patients and 24 control subjects. Peripheral blood samples from patients and controls were analyzed using 5-color flow cytometry. Apoptotic cells were detected using an Annexin V-FITC/7-AAD kit. There was a statistically significant decrease of all blood cells after the 131-I therapy. The CD19+ B lymphocyte population was the most affected (5.82 ± 3.21% before therapy vs. 3.93 ± 2.60% after therapy, p = 0.008). This decrease was correlated with the degree of apoptosis of peripheral blood lymphocytes (Spearman’s r = 0.563, p =0.013). We concluded that 131-I therapy of DTC patients led to a decrease of all peripheral blood cells, especially CD19+ B lymphocytes. This directly correlated with apoptosis of PBLs, indicating that radiation damage to B cells leads to subsequent elimination by apoptosis.