Bioisosteric modification on melatonin: synthesis of new naphthalene derivatives, in vitro antioxidant activity and cytotoxicity studies

Melatonin (MLT) is a strong free radical scavenger that protects the body from the deleterious effects of excess oxidants. Synthesis of MLT analogue compounds with antioxidant potency has recently attracted the interest of researchers. In general, the strategy consists of modifying the groups in the different sites of the indole ring or replacing the indole ring with an analogue. As part of our ongoing research, the antioxidant capacity and cytotoxicity of newly synthesized MLT analogue naphthalene derivatives were evaluated. The radical scavenging activity was tested by a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Most of the synthesized compounds showed significant antioxidant activity in comparison to MLT. The structure-activity relationship was identified. The in vitro cytotoxic effects of the synthesized compounds were also investigated in CHO-K1 cells using the MTT assay

Genetics of immunoglobulin-A vasculitis (Henoch-Schönlein purpura): An updated review

Immunoglobulin-A vasculitis (IgAV) is classically a childhood small-sized blood vessel vasculitis with predominant involvement of the skin. Gastrointestinal and joint manifestations are common in patients diagnosed with this condition. Nephritis, which is more severe in adults, constitutes the most feared complication of this vasculitis. The molecular bases underlying the origin of IgAV have not been completely elucidated. Nevertheless, several pieces of evidence support the claim that genes play a crucial role in the pathogenesis of this disease. The human leukocyte antigen (HLA) region is, until now, the main genetic factor associated with IgAV pathogenesis. Besides a strong association with HLA class II alleles, specifically HLA-DRB1 alleles, HLA class I alleles also seem to influence on the predisposition of this disease. Other gene polymorphisms located outside the HLA region, including those coding cytokines, chemokines, adhesion molecules as well as those related to T-cells, aberrant glycosylation of IgA1, nitric oxide production, neoangiogenesis, renin-angiotensin system and lipid, Pyrin and homocysteine metabolism, may be implicated not only in the predisposition to IgAV but also in its severity. An update of the current knowledge of the genetic component associated with the pathogenesis of IgAV is detailed in this review.Acknowledgements: RL-Mis supported by the Miguel Servet I programme of the Spanish Ministry of Economy and Competitiveness through the grant CP16/ 00033. FG is recipient of a Sara Borrell postdoctoral fellowship from the “Instituto Carlos III de Salud” at the Spanish Ministry of Health (Spain) (CD15/00095). SR-M is supported by funds from the RETICS Program (RIER) (RD16/0012/0009). FDC is supported by the Ramón y Cajal programme of the Spanish Ministry of Economy and Competitiveness through the grant RYC-2014-16458

Plasma interleukin-10 and interleukin-12 levels in patients with familial Mediterranean fever

PubMedID: 16397779Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever, polyserositis and arthritis. A vast array of cytokines were analysed in these patients, however, little is known about the pro-inflammatory cytokine interleukin (IL)-12. Plasma IL-12 and IL-10 were measured in 24 patients with FMF (19 active, 5 inactive) and 18 healthy controls by ELISA. From 15 active patients blood was also drawn in attack-free period. Mean plasma IL-12 levels of the FMF patients (mean ± SEM, 6.84±3.59 pg/ml) were higher than the controls (0.13±0.09 pg/ml, P<0.001). Mean IL-12 levels of active (7.02±5.23 pg/ml) and inactive patients (6.89±5.61 pg/ml) were comparable, and they were higher compared to controls (P ? 0.001). Mean plasma IL-10 levels of the total FMF patients (3.01±1.53 pg/ml) were also higher than the controls (P=0.024). Patients had higher IL-10 levels in attacks (3.83±2.02 pg/ml) compared to levels when they were in remission (1.86±1.59 pg/ml, P=0.046). Significantly elevated IL-12 levels in FMF patients regardless of activity may suggest the presence of a pro-inflammatory state also in the inactive period of FMF. Significant increase in IL-10 levels in FMF group may point to the compensatory suppression of inflammation in active periods of the disease. © Springer-Verlag 2006

Expression of soluble CD27 and interleukins-8 and -10 in B-cell chronic lymphocytic leukemia: Correlation with disease stage and prognosis

PubMedID: 17526459Investigators in this study explored levels of soluble CD27 (sCD27), interleukin (IL)-8, and IL-10 in B-cell chronic lymphocytic leukemia (B-CLL), and the correlation of these levels with disease stage and prognosis. Plasma IL-8, IL-10, and sCD27 levels were assessed with enzyme-linked immunosorbent assay tests in 22 healthy donors and 70 patients with B-CLL (49 men and 21 women). Mean patient age was 61.57 y (range, 44-75 y). Mean healthy donor age was 62.09 y (range, 40-72 y). In the study group, mean values were as follows: plasma IL-8, 284.758 pg/mL (0-1000 pg/mL); plasma IL-10, 26.152 pg/mL (0-100 pg/mL); sCD27, 731.357 U/mL (139.9-1000 U/mL); white blood cell count, 59.9 × 10 9/L (0.8-250.0 × 10 9/L); hemoglobin count, 11.2 g/dL (5.0-16.2 g/dL); platelet count, 162.5 × 10 9/L (29.8-317 × 10 9/L); B 2 microglobulin (B 2M) 3350.2 mg/L (274.7-7499.9 mg/L); CD38, 19.5%; and lactate dehydrogenase (count, 497.5 U/L (263.0-1507 U/L). Patients represented all Rai stages, with 22.9% at stage 0, 11.4% at stage I, 11.4% at stage II, 41.4% at stage III, and 12.9% at stage IV. Plasma levels of IL-8, IL-10, and sCD27 were correlated between study and control groups; significantly higher IL-8 (P=.001) and sCD27 (P=.000) levels were found, but the IL-10 level was not significant (P=.139). Plasma IL-10 (P=.01) and sCD27 (P=.008) were positively correlated with Rai stage, but IL-8 was not (P=.146). Levels of sCD27 were significantly correlated with values for B 2M (P=.000), hemoglobin (P=.028), lactate dehydrogenase (P=.001), CD19 (P=.03), and IL-10 (P=.000). IL-8 was significantly correlated with white blood cell (P=.000) count, and CD38 (P=.001) and CD5 (P=.006) levels. IL-10 was significantly correlated with B 2M (P=.017), CD19 (P=.000), platelet (P=.002), and CD27 (P=.000). In survival distributions for CD27, IL-8 and IL-10 were found to have more significant relationships for all parameters (P=.0000). In conclusion, the authors suggest that sCD27, IL-8, and IL-10 are more significant prognostic factors for B-CLL when compared with others, and these values should correlate with new prognostic factors (eg, zeta-associated protein-70, mutated/unmutated immunoglobulin variable heavy chain). ©2007 Health Communications Inc

Serum RANTES, MIP-1 alpha, and MCP-1 levels in Behcet's disease

WOS: 000231307100020PubMed ID: 16133585

Clinical significance of hepatocyte growth factor, platelet-derived growth factor-AB, and transforming growth factor-? in bone marrow and peripheral blood of patients with multiple myeloma

PubMedID: 17050506Angiogenesis is a process that plays an important role in the growth and progression of cancer; growing evidence suggests that neovascularization is important in hematologic malignancies. Increased angiogenic potential has been identified in multiple myeloma (MM). In this study, investigators simultaneously measured the levels of hepatocyte growth factor (HGF), platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor-alpha (TGF-?) through enzyme-linked immunosorbent assay in the bone marrow (BM) and peripheral blood (PB) of 30 patients with MM and 10 healthy controls. Differences in HGF values in BM sera were significant (P=.001) between patients and controls. In detailed analyses of HGF, PDGF-AB, and TGF-?, according to disease stage, a significant correlation was found between disease stage and BM HGF (P=.047), BM TGF-? (P=.021), and PB PDGF-AB (P=.006), respectively. When correlations between all other parameters were analyzed, significance was noted between PB TGF-? and lactate dehydrogenase (P=.02), PB TGF-? and PB HGF (P=.002), BM TGF-? and CD38 (P=.046), BM TGF-? and BM HGF (P=.000), BM TGF-? and BM PDGF-AB (P=.048), BM HGF and PB HGF (P=.044), and BM PDGF-AB and PB PDGF-AB (P=.000). BM HGF levels had a significant effect on overall survival, with disease severity assessed in terms of disease stage (P=.0018, log-rank test). These data show that in patients with MM, high levels of BM HGF, BM TGF-?, and PB PDGF-AB were associated with advanced disease stage; in addition, HGF played a significant role in disease processing and was related to disease severity. These findings have also led to the concept of a symbiotic relationship between the growth of myeloma cells and HGF, TGF-?, and PDGF-AB in BM. ©2006 Health Communications Inc

Serum endothelial leukocyte adhesion molecule-1 and intercellular Adhesion molecule-1 levels in rheumatoid artritis

Purpose: To investigate the serum levels of adhesion molecules, soluble endothelial adhesion molecule-1 (sELAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1), in active and inactive patients with rheumatoid arthritis (RA) and to find out their importance as a parameter in the active phase of the disease. Methods: sELAM-1 and sICAM-1 levels were measured in 30 active and 23 inactive RA patients, in 21 Behcet's disease (BD) patients and in 23 healthy subjects by using enzyme immunoassay (ELISA). Results: sELAM-1 levels of active RA patients were found to be increased than those of BD patients and healthy controls (p 0.05 for both). No differences were observed in the levels of sELAM-1 and sICAM-1 between active and inactive RA patients. There was a correlation between sELAM-1 and sICAM-1 levels in active RA patients and in healthy controls. Conclusion: It can be concluded that ELAM-1 and ICAM-1 may play roles in the pathogenesis of RA but cannot be used as disease activity parameters

Analysis of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) Promoter -318C/T and +49A/G Gene Polymorphisms in Turkish Patients with Familial Mediterranean Fever

PubMedID: 22923220Either the role of the adaptive immune system or the interaction between innate and adaptive immune systems in familial Mediterranean fever (FMF) is not clear so far. So, we planned to search for the interaction between the innate and adaptive immune systems in the pathogenesis of FMF by investigating polymorphism for CTLA-4 gene, which plays a role in controlling antigen presentation to T cells. We also aimed to investigate whether there is an association between -318C/T and +49A/G polymorphisms in the CTLA-4 gene and the main clinical features of the disease. 75 FMF patients and 179 controls were studied. Polymorphism was detected by the PCR-RFLP technique. The CT genotype and T allele frequencies of the -318C/T polymorphism and the haplotype frequency for the -318T/+49A in the CTLA-4 gene were higher in the FMF (21. 3, 21. 3, and 10. 7 %) when compared with the controls (10. 6, 10. 6, and 5. 3 %; P = 0. 029, 0. 044, and 0. 029). However, these differences did not reach a statistically significant level after the Bonferroni correction. A significant linkage disequilibrium was found between the -318C/T and +49A/G polymorphisms in the CTLA-4 gene (D' = 0. 997, r2 = 0. 027, P = 0. 0002). Genotype and carrier frequencies of the CTLA-4 gene +49A/G polymorphism were not significantly different between FMF patients and healthy controls. No association was found between the studied polymorphisms and the main clinical features of the disease. Our findings suggest that although not statistically significant, higher frequencies of CTLA-4 gene -318CT genotype, T allele, and -318T/+49A haplotype in FMF patients may be related to the non-autoimmune pathogenesis of FMF. © 2012 Springer Science+Business Media, LLC.Firat University Scientific Research Projects Management Unit: TF2004BAP3Acknowledgments This work was supported by a grant from the Cukurova University Scientific Research Projects Unit, Adana, Turkey (Project Nr: TF2004BAP3)

C5A receptor gene polymorphism in Turkish FMF patients: Significant associations with Henoch Schonlein purpura and V726A MEFV mutation

Annual European Congress of Rheumatology -- 37790 -- LISBON, PORTUGALWOS: 000224551401120

Interleukin-10 and -12 in human milk at 3 stages of lactation: A longitudinal study

PubMedID: 17660171This study was undertaken to analyze postpartum changes in concentrations of interleukin (IL)-10 and IL-12 through the 3 stages of lactation. A total of 87 human milk samples were collected from 29 healthy mothers during the colostrum (0-3 days), early milk (14-17 days), and mature milk (44-47 days) phases. Enzyme-linked immunosorbent assay tests were performed on the milk samples. IL-10 was detected in 7 and IL-12 in 4 of the colostrum samples. In the transitional milk samples, IL-10 was present in 4 and IL-12 in 2; however, both of these cytokines became undetectable in mature milk samples. The decrease in concentrations of IL-10 and IL-12 was statistically significant during the postpartum period (P=.001 and P=.024, respectively). IL-10 levels in the colostrum samples were higher than in the transitional samples (P=.018, with use of the post hoc test). No statistically significant differences between IL-12 levels were noted in the colostrum samples and the transitional samples (P=.068, with use of the post hoc test). A negative correlation was observed between concentrations of IL-10 in colostrum and the total number of pregnancies (R=-.401; P=.031). The findings of the present study suggest that mean concentrations of IL-10 and IL-12 are decreased in human milk as lactation continues through its 3 phases. ©2007 Health Communications Inc