Increased circulating platelet and endothelial-derived microparticles in patients with cardiac syndrome X.

BACKGROUND: Cardiac syndrome X (CSX) has been associated with endothelial dysfunction and inflammation. We conducted a case-control study to evaluate the association between plateletý and endothelial-derived microparticles (PMPs and EMPs), as specific quantitative plasma markers of endothelial dysfunction, and the presence of CSX. METHODS: The present study was conducted on 40 CSX patients and 19 healthy individuals. C-reactive protein (CRP), and hematological and biochemical parameters were evaluated. The MP concentration in platelet-poor plasma (PPP) was quantitatively determined through flow cytometry using specific anti-human CD31, CD41a, CD62E, and CD144 antibodies. RESULTS: The mean platelet volume (MPV) and positive CRP rate (≥ 3.8 mg/l) were higher in patients compared to controls (P = 0.020 and P = 0.010, respectively). The CD62E+, CD144+, and CD31+41- EMPs, as well as CD41+ and CD31+CD41+ PMPs showed significant increase in CSX patients compared to controls (P < 0.050). There were direct correlations between the mean percentage of detected EMPs and PMPs as well as between their expression intensity; however, a reverse correlation was seen between the percentage of MPs and CD144 and CD41. Moreover, the MP level was reversely associated with prothrombin time (PT) and partial thromboplastin time (PTT) values. Only CD31+CD41+ PMP was correlated with CRP. CONCLUSION: It seems that EMPs and PMPs increase in CSX, which may contribute to various processes involved in the development of this syndrome.

A novel adjuvant, the mixture of alum and naltrexone, augments vaccine-induced immunity against Plasmodium berghei.

We previously showed that the mixture of naltrexone (NLT), a general opioid antagonist, and alum, acts as an effective adjuvant in enhancing vaccine-induced T helper 1 (TH1) humoral immune responses against Toxoplasma gondii. Here, we tested the efficacy of the mixture of NLT and alum in the induction of immunity in response to blood stages of Plasmodium berghei (BSPb) as a model vaccine. BALB/c mice were divided into five vaccination groups. Mice in the experimental groups received the BSPb vaccine alone or in combination with the adjuvant alum, NLT or the alum-NLT mixture. Mice in the control group received PBS. All mice were immunized on days 0, 7 and 14. Two weeks after the last immunization, immune responses to Plasmodium berghei were assessed. Our results indicated that including the alum-NLT mixture as an adjuvant during vaccination increased the ability of the BSPb vaccine to enhance lymphocyte proliferation, shifted the immune response towards a TH1 profile and increased Plasmodium berghei-specific IgG2a. This resulted in improved protective immunity against Plasmodium berghei. In conclusion, administering alum-NLT mixture in combination with the BSPb vaccine enhanced the vaccine-induced immunity, and shifted the immune response toward TH1 pattern.

The Effects of Isoproterenol and Propranolol on Cytokine Profile Secretion by Cultured Tumor-infiltrating Lymphocytes Derived from Colorectal Cancer Patients.

OBJECTIVE: Anti-tumor immunity and cytokine profiles have important roles in the development of cancer. Norepinephrine (NE) release due to sympathetic activation leads to a Th2 deviation via the beta-2 adrenergic receptor Beta-2 adrenergic receptor (ß-2AR) and could increase cancer progression. This study intends to determine the effects of isoproterenol (ISO; beta-agonist) and propranolol (PRO; beta-antagonist) on the production of IFN-γ, IL-4, and IL-17. Cytokine levels have been examined in tumor-infiltrating lymphocytes (TILs) and peripheral blood mononuclear cells (PBMCs) of patients with colorectal cancer (CRC). The ß-2AR expression on lymphocyte subsets was also assessed. MATERIALS AND METHODS: In this experimental study, TILs were isolated from fresh CRC tissue and patient PBMCs were obtained just prior to surgery. The cells were cultured in medium for 72 hours. Concomitantly, cells were stimulated with 10 µg/ml phytohemagglutinin (PHA) alone or in the presence of either 1 µmol/L of PRO or 1 µmol/L ISO. The concentration of cytokines in the supernatants was measured by ELISA. Three-color flow cytometry was used to determine the expression of ß-2AR on the lymphocyte subsets. Statistical analyses were performed via paired or independent t-test. RESULTS: Levels of IFN-γ, IL-4 and IL-17 were elevated after PHA-stimulation of PBMCs and TILs. However, the elevation of IFN-γ and IL-17 production by TILs in response to PHA was significantly lower than PBMCs. In the presence of ISO, the IFN-γ/IL-4 ratio reduced in all groups, but this reduction was very low in TILs. Interestingly, the effects of PRO on cytokine production were, at least partially, comparable to those of ISO. Depressed levels of ß-2AR expression were demonstrated on CD4+IFN-γ+ and CD4+IL-17+ lymphocytes in patients' PBMCs and TILs. CONCLUSION: This study has demonstrated the effects of ISO and PRO on cytokine production by TILs and determined ß-2AR expression on these cells. ISO failed to induce a shift toward the expected Th2 cytokine profile in CRC patients' TILs, which might be due to the downregulation of ß-2AR expression on TILs. Additionally, in this study, PRO induced a shift to a Th2 profile in PBMCs.