Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet's disease.

AIM: Behçet's disease (BD) is asystemic immunoinflammatory disorder and the aetiopathogenesis is to be specified. Cytokines play a role in immune response and in many inflammatory diseases. The aim of this case-control study is to investigate serum pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), soluble IL-2 receptor (sIL-2R), IL-6, and chemokine IL-8 levels in patients with BD. We also determined the end product of lipid peroxidation (malondialdehyde (MDA)) in BD patients as an index for oxidative stress. METHODS: A total of 37 patients (19 men, 18 women) with BD (active, n = 17; inactive, n = 20) and 20 age-matched and sex-matched healthy control subjects (11 men, nine women) included in this cross-sectional, blinded study. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometer technique using the immulite chemiluminescent immunometric assay. Lipid peroxidation was evaluated by Wasowicz et aL The levels of cytokines and lipid peroxidation in the active period were compared with the inactive period of the disease. Results are expressed as mean +/- standard error. RESULTS: IL-1beta levels were below the detection limits of the assay (< 5 pg/ml) in all samples. Mean levels of MDA (8.1+/-0.7 micromol/l), sIL-2R (800+/-38 U/ml), IL-6 (12.6+/-1.1 pg/ml), IL-8 (7.2+/-0.4 pg/ml), and TNF-alpha (7.9+/-0.5 pg/ml) in active BD patients were significantly higher than those in inactive patients (4.3+/-0.5 micromol/l, p < 0.01; 447+/-16 U/ml, p < 0.001; 8.3+/-0.6 pg/ml, p = 0.006; 5.3+/-0.1 pg/ml, p < 0.001; and 5.1 0.2 pg/ml, p < 0.001; respectively) or control subjects (2.1+/-0.2 micromol/l, p < 0.001; 446+/-20 U/ml, p < 0.001; 6.4+/-0.2 pg/ml, p < 0.001; 5.4+/-0.1 pg/ml, p < 0.001; and 4.7+/-0.1 pg/ml, p < 0.001, respectively). On the contrary, only the mean IL-6 level was significantly different between inactive BD and control subjects (p = 0.02). All acute phase reactants were significantly higher in active BD than in inactive period (for each, p < 0.01). Conclusions: High levels of sIL-2R, IL-6, IL-8 and TNF-alpha indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF-alpha seem to be related to disease activity. Increased lipid peroxidation suggests oxidative stress in BD and therefore tissue damage in such patients. Amelioration of clinical manifestations would be envisaged by targeting these cytokines, chemokines and lipid peroxidation with pharmacological agents

Adenosine deaminase enzyme activity is increased and negatively correlates with catalase, superoxide dismutase and glutathione peroxidase in patients with Behçet's disease: original contributions/clinical and laboratory investigations.

AIM: Behçet's disease (BD) is an inflammatory vasculitis with immunologic, endothelial and neutrophil alterations. Adenosine deaminase (AD) is a marker of T-cell activation and is related to the production of reactive oxygen species by neutrophils with the production of NO(*), O(2)(*-), H(2)O(2) and OH(*). We reported increased tumour necrosis factor-alpha, soluble interleukin-2 receptor, interleukin-6, interleukin-8 and NO(*) in active BD. As there is a relation between cytokines, T cells and oxidative stress in inflammatory diseases, this study further evaluated: (1) plasma AD activity and its correlation with acute phase reactants; (2) thiobarbituric acid-reactive substances (TBARS) as an indicator for lipid peroxidation; and (3) antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase in patients with BD. The effect of disease activity and correlations between the measured parameters were explored. METHODS: A total of 35 active (n=17) or inactive (n=18) patients with BD (16 men, 19 women) satisfying International Study Group criteria, and 20 age-matched and sex-matched controls (nine men, 11 women) were included in this cross-sectional case-control study. AD and TBARS were measured in plasma, catalase in red blood cells (RBC), and SOD and GSHPx in both plasma and RBC in both groups. Acute phase reactants (alpha(1)-antitrypsin, alpha(2)-macroglobulin, neutrophils, erythrocyte sedimentation rate) were used to classify patients as active or inactive. RESULTS: Plasma AD (mean+/-standard error of the mean, 36.1+/-0.7 U/l) and TBARS (4.2+/-0.1 nmol/ml) levels were significantly (for each, p<0.001) higher in BD than in controls (24.1+/-0.8 U/l and 1.6+/-0.1 nmol/ml, respectively). RBC catalase activity was significantly (p<0.001) lower in BD than in controls (120.9+/-3.8 versus 160.3+/-4.1 k/g haemoglobin). SOD and GSHPx activities were significantly lower in both plasma and erythrocytes of patients with BD than in controls (plasma SOD, 442.4+/-8.6 versus 636.4+/-9.2 U/ml, p<0.001; RBC SOD, 3719.2+/-66.0 versus 4849.7+/-49.0 U/g haemoglobin, p<0.001; plasma GSHPx, 73.1+/-1.5 versus 90.6+/-2.9 U/ml, p<0.001; RBC GSHPx, 600.7+/-8.0 versus 670.6+/-10.1 U/g haemoglobin, p<0.001). Active BD patients had significantly lower antioxidant enzymes (except RBC catalase) and higher AD and TBARS levels than inactive subjects (for each, p<0.01). When considering all BD patients, a significant positive correlation was present between AD and TBARS (p<0.001) whereas both AD and TBARS were negatively correlated with antioxidant enzymes (for each, p<0.05). CONCLUSIONS: AD and lipid peroxidation are increased and associated with defective antioxidants in BD, suggesting interactions between activated T cells and neutrophil hyperfunction. Measures of pro-oxidative stress and antioxidative defence with AD activity as an indicator of T-cell activation can be considered as significant supportive diagnostic indicators, especially in active disease. In addition, strengthening the antioxidant defence may contribute to treatment modalities

Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

OBJECTIVES: Serotonin plays a central role in ejaculation and selective serotonin reuptake inhibitors have been successfully used to treat premature ejaculation. Here, we evaluated the relationship between a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response of patients with premature ejaculation to SSRI medication. METHODS: Sixty-nine premature ejaculation patients were treated with 20 mg/d paroxetine for three months. The Intravaginal Ejaculatory Latency Time and International Index of Erectile Function scores were compared with baseline values. The patients were scored as having responded to therapy when a 2-fold or greater increase was observed in Intravaginal Ejaculatory Latency Time compared with baseline values after three months. Three genotypes of 5-HTTLPR were studied: LL, LS and SS. The appropriateness of the allele frequencies in 5-HTTLPR were analyzed according to Hardy-Weinberg equilibrium using the χ2-test. RESULTS: The short (S) allele of 5-HTTLPR was significantly more frequent in responders than in nonresponders (

Neuroprotective effect of edaravone in experimental glaucoma model in rats: a immunofluorescence and biochemical analysis

AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in rats. METHODS: In this study, 60 Wistar albino rats were used. Experimental glaucoma model was created by injecting hyaluronic acid to the anterior chamber once a week for 6wk in 46 of 60 subjects. Fourteen subjects without any medication were included as control group. Edaravone administered intraperitoneally 3 mg/kg/d to the 15 of 30 subjects starting at the onset of glaucoma induction and also administered intraperitoneally 3 mg/kg/d to the other 15 subjects starting at three weeks after the onset of glaucoma induction. The other 16 subjects who underwent glaucoma induction was administered any therapy. Retinal ganglion cells (RGCs) have been marked with dextran tetramethylrhodamine (DTMR) retrograde at the end of the sixth week and after 48h, subjects were sacrificed by the method of cardiac perfusion. Alive RGC density was assessed in the whole-mount retina. Whole-mount retinal tissues homogenized and nitric oxide (NO), malondialdehyde (MDA) and total antioxidant capacity (TAC) values were measured biochemically. RESULTS: RGCs counted with Image-Pro Plus program, in the treatment group were found to be statistically significantly protected, compared to the glaucoma group (Bonferroni, P<0.05). The neuroprotective activity of edaravone was found to be more influential by administration at the start of the glaucoma process. Statistically significant lower NO levels were determined in the glaucoma group comparing treatment groups (Bonferroni, P<0.05). MDA levels were found to be highest in untreated glaucoma group, TAC levels were found to be lower in the glaucoma induction groups than the control group (Bonferroni, P<0.05). CONCLUSION: Systemic administration of Edaravone in experimental glaucoma showed potent neuroprotective activity. The role of oxidative stress causing RGC damage in glaucoma was supported by this study results

Effects of Cigarette Smoke on Tissue Trace Element Concentration of Rats Exposed to Second-hand Smoke

Trace elements have an important effect on and play a key role in a variety of the processes necessary for life. Studies have indicated a definite correlation between content of trace elements and many common diseases. It has been concluded that smoking may be a substantial source of intake of these hazardous elements, not only to the smoker, but to nonsmokers via passive smoke, as well. Even passive intake of such elements can change the metabolism of other trace elements and influence their concentrations. In order to assess their potential role in some human diseases, it is necessary to measure trace element concentrations in various tissues in experimental models. In this study, liver, kidney and spleen tissue samples from rats exposed to secondhand smoke were analysed for Fe, Cu, Zn, Cr, Mn and Co trace element levels by atomic absorption spectrophotometer. Cr, Mn, Fe and Co levels in the liver, Fe and Co levels in the kidney, and Zn, Cu, Mn and Co levels in the spleen were significantly lower than those of controls, but Cu levels in the kidney and Fe levels in the spleen were significantly higher than those of controls. Our data suggest that chronic exposure to cigarette smoke alters the trace element concentration of various tissues in rats exposed to secondhand smoke. These alterations may be attributable to oxidative stress produced by cumulative effect of inhaled smoke rather than the toxic effect of absorbed toxic metals. Low Mn levels in the liver and spleen, increased Cu levels in kidney and Fe levels in the spleen, and changes in the metabolism of Zn, Fe and Cu may be indicators of oxidative stress. Decreases in Co and Cr levels in rats exposed to secondhand smoke may also be related to the intake of the toxic trace elements present in cigarette smoke. [Med-Science 2012; 1(1.000): 1-12

Effects of the general anaesthetic agent, propofol, on erythrocyte deformability

Arslan, Mustafa/0000-0003-4882-5063WOS: 000276730200003PubMed: 20437820Objectives: Propofol is an anesthetic agent frequently used for sedation and general anesthesia. The purpose of our study was to investigate the effect of propofol, a general anesthetic, on erythrocyte deformability in rats. Methodology: The study was performed on 20 male and 20 female rats, with 10 rats in each study group and 10 rats in each control group. The rats in the study group were administered propofol (150 mg.kg(-1)) intraperitoneally, and the rats in the control group were administered SF. Erythrocyte packs were prepared using heparinized total blood samples. Deformability measurements were done by erythrocyte suspensions in PBS buffer. A constant flow filtrometer system was used to measure erythrocyte deformability, and the relative resistance was calculated. Results: The use of propofol resulted in the increase in the relative resistance, which is an indicator for the erythrocyte deformability in both male and female rats (p=0.002, p=0.042, respectively). Conclusion: A negative change in the erythrocyte deformability may cause a functional deterioration in blood flow and tissue perfusion (Fig. 1, Ref. 23). Full Text (Free, PDF) www.bmj.sk

Synovial nitric oxide concentrations are increased and correlated with serum levels in patients with active Behcet's disease: a pilot study

Behcet's disease (BD) is a relapsing immuno-inflammatory vasculitis of unknown etiology characterized by endothelial dysfunction. Articular symptoms and signs are present in about 75% of cases and characterized by seronegative arthritis and nonspecific synovitis. We demonstrated that both serum and erythrocyte nitric oxide (NO center dot) levels, the most abundant free radical in the body, were elevated in BD and associated with disease activity. This study further investigated NO center dot levels in the synovial fluid and serum from patients with active and inactive BD. A total of 23 BD patients with articular involvement ( 14 men and 9 women) satisfying International Study Group criteria and 15 age- and sex-matched healthy control subjects ( 9 men and 6 women) undergoing elective arthroscopy were included in this case-control investigation. The synovial fluid and serum were obtained from BD patients and controls. Clinical and laboratory findings including neutrophil count and erythrocyte sedimentation rate (ESR) were used to classify BD patients as active (n = 11) or inactive (n = 12). Synovial as well as serum NO center dot levels were compared between the groups and correlation analysis was performed. Acute phase reactant levels were significantly higher ( for each, p 0.05). Active BD patients had significantly higher serum NO center dot levels ( 38.84 +/- 9.15 mu mol/l) than inactive patients (30.91 +/- 5.88 mu mol/ l, p = 0.018) and control subjects (28.86 +/- 5.91 mu mol/ l, p=0.002). In addition, synovial NO center dot levels were positively correlated with serum levels (r(2) = 0.621, p< 0.001). Increased synovial NO center dot levels in active BD patients probably reflect a nonspecific inflammatory process of the synovium and, therefore, arthralgia and arthritis as a common finding of BD