Inhibitory effect of adenosine on intimal hyperplasia and proliferation of smooth muscle cells in a carotid arterial anastomosis animal model.

PURPOSE: The effect of adenosine (9-ß-0-ribifuranosyladenine) on the endothelial cell proliferation and neointimal hyperplasia is investigated in the rabbit carotid artery anastomosis model. METHODS: Twenty-eight New Zealand white rabbits were arranged in four groups of seven animals each. The right carotid arteries of each animal were transsected and re-anastomosed. The left sides remained as control. In Group A, no medication was used. In Group B, subcutaneous Adenosine was applied for 3 days. In Group C, the same dose was applied for 7 days, and in Group D for 21 days. After 28 days, the luminal diameters, luminal areas, intima/media ratios were all measured by using histopathological evaluation. FINDINGS: The mean luminal diameters and areas of the four groups were smaller than the control ones. Massive thickening of smooth muscle cell proliferation and dense intensifying in the connecting tissues were observed most prominently in Group A, in decreasing degrees within other groups. Intima/media ratio was highest in Group A. Scoring the quantity of e-NOS positive staining also revealed a significant difference between the experimental groups and their control associates. CONCLUSION: The process of endothelial cell proliferation and neointimal hyperplasia can be significantly reduced by the use of adenosine.

Synthesis and anti-inflammatory activities of novel 5-(3,4-dichlorophenyl)-3-[(4-substitutedpiperazin-1-yl)methyl]-1,3,4-oxadiaxole-2(3H)-thiones.

To synthesize a new series of 5-(3,4-dichlorophenyl)-3-[(4-substitutedpiperazin-1-yl)methyl]-1,3,4-oxadiaxole-2-thiones for their anti-inflammatory activity.The title compounds synthesized by Mannich reaction of prepared 5-(3,4-dichloro-phenyl)-1,3,4-oxadiazole-2-thione and appropriate substituted piperazine derivatives. The structures of the compounds were confirmed by IR, NMR and elemental analyses. The newly synthesized compounds were evaluated for their anti-inflammatory and ulcerogenic activities.Most of the compounds were found to have significant anti-inflammatory profile in carrageenan footpad edema test. The compounds showed anti-inflammatory activity ranging from 30.6% to 57.8% inhibition.The compounds 5b, 5f, 5i, 5p and 5r showed most prominent anti-inflammatory activity with low gastric ulceration incidence than the reference drug indomethacine. These compounds could serve as lead molecules for further modifications.

Is there an association between serum 25-hydroxyvitamin D concentrations and disease activity in rheumatoid arthritis?

BACKGROUND: Recently, it has been recognized that vitamin D not only is important for calcium metabolism and maintenance of bone healthy, but also plays an important role in reducing risk of many chronic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus, insulin-dependent diabetes mellitus, multiple sclerosis, several cancers, heart and infectious diseases. In RA, the role of vitamin D is undefined. METHODS: The objective of this present study was to determine serum 25-hydroxyvitamin D (25(OH)D) concentrations in patients with RA and to establish its correlation with disease activity. This study was performed on fifty-five consecutive patients RA fulfilling the American Collage of Rheumatology (ACR) criteria for the classification of RA and forty-five healthy subjects. Serum 25(OH)D levels were measured using Elecsys 25(OH)D reactive kit. Disease activity was assessed according to DAS28, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The association between serum levels of 25(OH)D and age, gender, disease duration and disease activity parameters were established. RESULTS: The mean serum 25(OH)D levels were significantly decreased in RA patients compared to healthy controls (p < 0.01) and were associated with higher levels of parathyroid hormone. Vitamin D deficiency (i.e. < 30 ng/ml) was found in 50 patients (90.9 %). Serum levels of vitamin D lower than 20 ng/ml were found in 72 % of patients. We did not find the correlation between serum 25(OH)D levels and disease activity parameters. CONCLUSIONS: Our findings have demonstrated that serum 25(OH)D levels is highly prevalent in patient with RA. We believe that it will be helpful to investigate the vitamin D levels in order to determine the osteomalacia risk of RA patients (Tab. 2, Ref. 11).

Can the patient-reported outcome instruments determine disease activity in rheumatoid arthritis?

OBJECTIVES: The aim of this study was to investigate the indicative value of the patient-reported outcome instruments (PROs) on disease activity in rheumatoid arthritis (RA). METHODS: Three hundred sixty eight patients with RA were included in this cross-sectional study. Disease activity was evaluated using both the Disease Activity Score 28 (DAS 28) and the Clinical Disease Activity Index (CDAI). Patients who had DAS 28 score < 3.60 points and CDAI score <10.00 points were allocated into the "low disease activity" group and those who had DAS 28 score > or = 3.60 points and CDAI score > or = 10.00 points into the "moderate or high disease activity" group. The Health Assessment Questionnaire (HAQ), Nottingham Health Profile (NHP), Rheumatoid Arthritis Quality of Life (RAQoL), and Short Form 36 (SF 36) were used as PROs. Logistic regression analysis was used to find variables, which had an indicative value for disease activity. RESULTS: HAQ, pain and emotional reaction subscales of NHP, and bodily pain, general health and social functioning subscales of SF 36 had independent indicative values, when DAS 28 was used as dependent variable. On the other hand, HAQ, pain and emotional reaction subscales of NHP, and general health and emotional role limitation subscales of SF 36 had indicative values when CDAI was used as dependent variable. DAS 28 and CDAI both showed HAQ as the parameter with the highest odds ratio (OR). But RAQoL had shown no independent indicative value for projecting disease activity. CONCLUSION: It was concluded that HAQ could determine disease activity in RA better than other PROs included in this study (Tab. 4, Ref. 36).

Correlation between soluble intercellular adhesion molecule 1 level and extracellular superoxide dismutase activity in rheumatoid arthritis: a possible association with disease activity.

OBJECTIVE: We investigated serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and the activity of extracellular superoxide dismutase (EC-SOD) in rheumatoid arthritis (RA). We also considered whether there was a correlation between sICAM-1 and EC-SOD and disease activity. METHODS: Levels of sICAM-1 were measured in serum from 42 patients with active RA and 30 control subjects by enzyme-linked immunosorbent assay (ELISA). EC-SOD activity was determined in sera isolated from patients with active RA and from controls. RESULTS: The serum levels of sICAM-1 were significantly higher in patients with RA than in control subjects (p<0.001). In contrast, the activity of EC-SOD was significantly lower in RA patients than in healthy controls (p<0.001). A significant negative correlation was found between the levels of sICAM-1 and EC-SOD activity (r=-0.39, p<0.01). There was a statistically positive correlation between sICAM-1 levels with Ritchie articular index (RAI) score and C-reactive protein (CRP) (r=0.32, p<0.05; r=0.44, p<0.01, respectively). CONCLUSIONS: These results show that the increased levels of sICAM-1 present in active RA patients might be due to the decreased activity of EC-SOD, and increased levels of sICAM-1 may also reflect disease status or activity.

Effects of coronary artery bypass grafting on cellular immunity with or without cardiopulmonary bypass: changes in lymphocytes subsets.

Cell-mediated immunity responses decrease after all kinds of surgical procedures. Either anesthesia or surgical trauma plays an important role in this effect. Identification of functional lymphocyte subsets, by using appropriate monoclonal antibodies and analysis of flow cytometry data, appears to provide an accurate measurement of cellular immune competence. We found a significant decrease in the total number of T helper/inducer cells (p<0.035), B cells (p<0.043) and natural killer cells (NK) (p<0.018) but in contrast, increase in NK cell activity (p<0.012) in the peripheral arterial blood of ten patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (group 1) immediately after surgery and postoperative day 1 (POD1). On the other hand, there was no significant change of these parameters occurred in the peripheral arterial blood of ten patients (group 2) who were undergoing coronary artery bypass grafting without cardiopulmonary bypass. Therefore, we conclude that coronary artery bypass grafting (CABG) with cardiopulmonary bypass induce a greater decrease in immunologic response than CABG without cardiopulmonary bypass (off pump) operations. Nevertheless, off pump CABG operations do not induce a greater decrease in immunologic response than other surgical operations.

Sister chromatid exchange analysis in the lymphocytes of patients with ankylosing spondylitis.

OBJECTIVE: This study investigated whether any genomic change occurs in DNA level in ankylosing spondylitis (AS) by measuring sister chromatid exchange (SCE) frequency. METHODS: SCE frequency was detected on metaphase chromosomes obtained from peripheral blood lymphocyte cultures in 15 patients diagnosed as having AS. SCE values were also obtained from 15 healthy subjects as a control group. SCE frequencies were detected from metaphases obtained from standard blood cultures by using bromodeoxyuridine and staining by Giemsa. RESULTS: SCE frequencies of AS were statistically higher than those of the control group (p < 0.005). CONCLUSION: These results suggest that genetic factors may play a more important part than realised in the aetiology of AS.