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Background Endothelial dysfunction plays an important role in pathogenesis of systemic lupus erythematosus (SLE). Considering the importance of serum soluble vascular cell adhesion molecule-1 as the most abundant of the circulating adhesion molecules increased as a result of endothelial dysfunction and the role of endothelin-1 in pathophysiology of SLE, this study aimed to evaluate serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels in SLE patients compared to healthy subjects. Methods In this cross-sectional study, 60 SLE patients according to the Systemic Lupus International Collaborating Clinics classification criteria for SLE and 40 age and sex-matched healthy controls were included. In patients, clinical examination was performed and SLE disease activity index was assessed. Serum endothelin-1 and soluble vascular cell adhesion molecule-1 levels were measured using ELISA kits. Results The mean ± standard deviation age of patients and controls was 31.91 ± 7.66 and 33.20 ± 10.08 years, respectively. Compared to healthy controls, serum soluble vascular cell adhesion molecule-1 (1023.8 ± 352.96 vs. 866.06 ± 109.91) and endothelin-1 (77.83 ± 16.27 vs. 54.45 ± 12.01) was significantly higher in SLE patients ( P = 0.003 and P < 0.001, respectively). The most common organs involved in patients were skin, joint and kidney. There were no significant differences in serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels according to organ involvement, activity of disease and the conventional serum markers of disease activity ( P > 0.05). There was no significant correlation between disease activity, organ involvement and negative or positivity of autoantibodies as well as serum complement with endothelin-1 and vascular cell adhesion molecule-1 levels ( P > 0.05). Conclusions Although our study revealed higher serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels in SLE patients compared to healthy controls, there were no significant correlations between their serum levels with organ involvement and disease activity.

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BACKGROUND: Kidney transplantation is the treatment of choice for patients with end-stage renal disease. OBJECTIVE: To evaluate the changes in serum soluble TNF-like weak inducer of apoptosis (sTWEAK) and fibroblast growth factor 23 (FGF-23) in hemodialysis (HD) patients and renal transplant recipients (RTR). METHODS: Serum samples were obtained from 30 patients on chronic HD, 30 RTRs, and 30 normal controls. Biochemical factors, sTWEAK, FGF-23, and interlukin-6 (IL-6) were measured by standard methods. RESULTS: Serum levels of sTWEAK in RTRs were significantly higher than those in the HD patients (p=0.025); RTR and HD patients had significantly lower sTWEAK levels than the controls (p=0.001 and p= 0.038, respectively). Serum levels of FGF-23 in HD patients were significantly (p=0.001) higher than those in the RTR; the level was higher in both studied groups compared to that in the controls (p=0.001 for both groups). The mean serum level of IL-6 in HD was significantly higher than that in RTR patients (p=0.013). IL-6 levels in both groups were significantly higher than those in controls (p=0.001 and p= 0.012, respectively). In HD group a negative correlation was found between FGF-23 and sTWEAK (r= 0.375, p=0.041); there were also a significant correlation between FGF-23 and IL-6 (r= 0.480, p= 0.007) and between IL-6 and sTWEAK (r= 0.409, p=0.025). CONCLUSION: We found that serum sTWEAK is decreased and FGF-23 is increased in HD and RTR groups comparing with the control group. However, further studies are needed to shed light over their direct role on atherosclerosis and cardiovascular outcomes.

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BACKGROUND: Many adverse effects have been reported on using cyclosporine (CSA) in organ transplantation. OBJECTIVE: To investigate the effects of CSA on paraoxonase (PON) activity and lipid peroxidation metabolites in early and late-stage of peroxidation and also total antioxidant (TA). METHODS: Twenty 220-250 g adult male Wistar rats were included in the study. The animals were stored for one week in the animal room before the initial injection to habituate with temperature, humidity, and circadian rhythm of day (12 h) and night (12 h). The temperature was kept at 23 °C. Animals had access to food and water ad libitum. RESULTS: A significant (p=0.002) increase in the serum levels of conjugated diones was observed in the case compared to the control group. At the end of the study, malondialdehyde (MDA) levels in CSA group was significantly (p=0.01) higher than the control group. Serum PON1 activity was significantly (p=0.004) lower in the case than the control group. CONCLUSION: CSA administration could impair oxidant-antioxidant pathways and increase oxidative stress. Antioxidant therapy could be beneficial in patients treated with CSA.

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BACKGROUND: Cyclosporine therapy is associated with a variety of adverse effects. Recent studies have suggested increased oxidative stress as a cause of these side effects. OBJECTIVE: Since, melatonin is one of the most powerful known antioxidants, and considering that isoproterenol is one of the drugs stimulating endogenous melatonin production, we tried to determine the effect of isoproterenol on LDL susceptibility to oxidation and serum total antioxidant capacity in cyclosporine-treated rats. METHODS: 32 male Wistar rats were divided into four groups: group A were controls that received placebo; group B received intraperitoneal isoproterenol (20 mg/kg/d) alone; group C received intravenous cyclosporine (15 mg/kg/d) alone; and group D received both drugs simultaneously at the same doses and durations-cyclosporine one week after administration of isoproterenol. Blood samples were drawn four times from rats in each group: before injections, during the treatment, end of the treatment, and one week after the last injections. RESULTS: There was a significant (p<0.05) increase in LDL susceptibility to oxidation, and a decrease in serum total antioxidant capacity (p<0.05) in group C rats. But, there were no significant changes in group B and D rats in terms of LDL susceptibility to oxidation and total antioxidant capacity. CONCLUSION: Isoproterenol may be capable of delaying adverse effects of cyclosporine by preventing the increase in LDL susceptibility to oxidation, and decrease in serum total antioxidant capacity.

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BACKGROUND: Oxidative stress is the main mechanism resulting in cyclosporine-induced nephrotoxicity. Because of its ability to stimulate endogenous melatonin production, isoproterenol is one of the most powerful antioxidant drugs. In this study, we sought to determine the effect of isoproterenol on cyclosporine-induced nephrotoxicity in rats. MATERIALS AND METHODS: Thirty two young male Wistar rats were divided into four groups: of group A were controls that received placebo; group B, received intraperitoneal isoproterenol (20 mg/kg/d) alone; group C, intravenous cyclosporine (15 mg/kg/d) alone; and group D, both drugs simultaneously at the same doses and durations namely cyclosporine 1 week after administration of isoproterenol. Blood samples to measure serum urea, creatinine, and melatonin levels were drawn four times for each group: before injection, at the mid period of treatment, at the end of treatment, and 1 week after the last injections. RESULTS: Isoproterenol increased mean serum melatonin level in groups B and D rats (P < .05). With regard to deteriorated renal function [DRF = (urea + creatinine)/2], administration of cyclosporine with (group D) or without (group C) isoproterenol was associated with decreased renal function (P < .05), although it was more perturbed in the latter instance. Measured DRF at the middle and the end of drug administration periods of A and B (revealed significant differences compared with groups C and D; P < .05). DISCUSSION: Although cyclosporine-induced nephrotoxicity is not completely eliminated by isoproterenol, the latter showed some protective effects.

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BACKGROUND: As renin-angiotensin system (RAS) activity may affect the severity of oxidative stress and inflammatory markers, we assessed the effects of enalapril (E) and/or losartan (L) on these markers in renal transplant recipients with RAS polymorphisms. PATIENTS AND METHODS: After determination by PCR of RAS genotypes, consisting of the angiotensin-converting enzymes (ACE I/D), angiotensinogens (AGT M235T) and angiotensin II type 1 receptors (ATR1 A1166C), 76 recipients were recruited randomly and assigned 4 groups. The first (n = 17) and second (n = 24) groups were treated with E (E(+): 10 mg/d) and L (L(+): 50 mg/d) alone, respectively. The third positive control group (n = 17) received E + L (E(+)L(+): 10 mg/d + 50 mg/d) and the fourth negative control group (n = 18) received no medication (E(-):L(-)). High-sensitivity C-reactive protein (hs-CRP) and total antioxidant (TA) inflammatory and antioxidative markers were measured after 2 months. After a 2-week washout period, the E(+) group was changed to L(+) and vice versa in a crossover design. They were followed for another 8 weeks before retesting hs-CRP and TA. A value of P < or = .05 was considered significant. RESULTS: After 2 and 4 months of treatment with the drug regimen, hs-CRP and TA levels were significantly decreased and consequently increased among the E(+)L(+), L(+) and E(+) groups (P < .05). On analyzing the relationship between RAS polymorphisms and baseline hs-CRP or TA levels, CC genotype of ATR1 showed lower hs-CRP levels (P = .04). However, none of the RAS polymorphisms predicted the antioxidant and anti-inflammatory response rates to the drugs (P > .05). CONCLUSION: Although hs-CRP was lower in the CC genotype patients of ATR1 polymorphisms E and/or L reduced hs-CRP and increased TA regardless of the RAS genotype.

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OBJECTIVE: Lipoprotein a [Lp(a)] is a strong biochemical risk factor that predicts posttransplant atherosclerosis. In this study we measured the ankle to arm blood pressure index (AAI) as a predictor of clinical atherosclerosis and assessed its relationship to serum Lp(a) values among 60 renal transplant recipients. MATERIALS AND METHODS: After measuring the AAI in a recumbent position, biochemical factors including cholestrol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and Lp(a) were measured by commercial kits in 60 renal transplant and 30 healthy subjects. Results were analyzed using SPSS. RESULTS: Lp(a) concentrations were significantly higher among transplant recipients compared with the control group (P < .05). AAI was similar between the kidney transplant recipients and controls, showing no significant correlation of Lp(a) concentration with AAI. CONCLUSION: Increased serum Lp(a) in renal transplant recipients, a potent biochemical risk factor for atherosclerosis, was not associated with abnormal AAI.

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INTRODUCTION: In this study, hemoglobin (Hb) concentrations secondary to enalapril (E) or losartan (L) therapy were evaluated with respect to renin-angiotensin system (RAS) polymorphisms in renal transplant recipients. MATERIALS AND METHODS: After determination of RAS polymorphisms [angiotensin-converting enzyme (DD, non-DD), angiotensinogen (TT, non-TT), and angiotensin receptor type 1 (CC, non-CC)] by polymerase chain reaction, 70 renal transplant recipients were recruited to four groups randomly: first and second groups were treated with E (10 mg/d, 15 patients) and L (50 mg/d, 20 patients) alone, respectively. The third group received E+L (10 mg/d + 50 mg/d, 13 patients) and the fourth group (22 patients) received no medication. The treatment protocol was followed for 16 weeks. Complete blood counts were checked before treatment and every 2 months. P<.05 was considered to indicate statistical significance. RESULTS: Treatment for 4 months decreased the Hb level in the E+L (14.15 +/- 0.94 to 12.06 +/- 0.66 g/dL, P=.000), E (14.00 +/- 0.86 to 13.11 +/- 0.82 g/dL, P=.02), and L (14.12 +/- 0.90 to 12.10 +/- 2.35 g/dL, P=.01) groups, but not in the control group (13.55 +/- 0.70 to 13.36 +/- 0.69 g/dL, P>.05). None of these regimens showed greater Hb reduction than the others (P>.05). None of the RAS polymorphisms predicted the intensity of the reduced Hb according to the type of treatment (P>.05). Any other sets of RAS polymorphisms (alone or together) did not impact on Hb levels pre- or post-intervention (P>.05). CONCLUSION: Our findings suggest that low dosages of E and/or L decrease Hb levels regardless of the RAS polymorphisms.

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Increased serum lipoprotein(a) is an independent risk factor for atherosclerosis in renal transplant recipients. Higher levels may be due to genetic factors, for example, apolipoprotein A isoforms and/or environmental states such as drugs and diets. We evaluated 75 renal transplant recipients including 30 men and 45 women of overall mean age of 30 +/- 7 years and transplantation duration of 57 +/- 10 months as well as 30 healthy controls for apolipoprotein A isoforms, lipoprotein(a) concentrations, serum triglycerides, serum cholesterol, serum creatinine, and serum homocysteine concentrations. High- and low-molecular-weight apolipoprotein A isoforms (>35 and <35 kringle 4) were observed in 71% and 29% of renal transplant recipients and 83% and 17% of controls. Average lipoprotein(a) concentration ratios between high- and low-molecular-weight apolipoprotein A isoenzymes were significantly greater in renal transplant recipients than in controls. Lipoprotein A and cholesterol concentrations that did not correlate with each other were not higher among the eight renal transplant recipients with creatinine levels greater than 1.8 mg/dL. Absolute levels in renal transplant recipients with failed grafts also were not different regarding the various apolipoprotein A phenotypes. Homocysteine levels were significantly higher with high-molecular-weight apolipoprotein A isoenzymes. A relationship existed between lipoprotein(a) and triglycerides, but not cholesterol: higher triglyceride levels were associated more with high-molecular-weight isoforms of apolipoprotein A (P = .027). Lipoprotein(a) concentrations are higher in low-molecular-weight isoforms of apolipoprotein but triglyceride levels and homocysteine concentrations are higher among the high-molecular-weight isoforms of apolipoprotein A. This finding could be used as a guideline to select the most appropriate drug for different apolipoprotein A isoforms.

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Atherosclerosis may be evaluated by structural or functional changes of the main arteries. We sought to investigate the probable associations of static and dynamic arterial changes with lipoprotein (a) and homocysteine levels, the two risk factors for atherosclerosis. Intima-media thickening and vasodilatory responses to nitroglycerine of the common carotid artery and the renal transplant artery were studied by color Doppler sonography in 75 renal transplant recipients and 30 controls. At 3, 5, and 10 minutes after 0.4 mg of sublingual nitroglycerine are measured resistive index and peak systolic velocity of the common carotid artery and renal transplant artery. Intima-media thickening in renal transplant recipients and controls were 0.86 +/- 0.34 mm and 0.74 +/- 0.14 mm (P = .05), respectively. Although intima-media thickness did not correlate with the duration of renal transplantation, it was significantly higher in older renal transplant recipients. Peak systolic velocity of common carotid artery was significantly decreased by nitroglycerine in the controls (81.8 +/- 16.7 m/s to 73.2 +/- 12.8 m/s, P = .03). This decrement was more obvious in renal transplant recipients, especially at 10 minutes (69.6 +/- 18.5 m/s vs 59.3 +/- 2 m/s, P = .01). These reductions did not correlate with intima-media thickening, latter of which also did not correlate with homocysteine concentrations, which were higher among renal transplant patients with creatinine more than 1.8 mg/dL. Basal resistive indices of the common carotid artery and renal transplant artery were higher among graft recipients with dysfunction than recipients with good function, (0.7 vs 0.59, P = .003). In conclusion, neither homocysteine nor lipoprotein(a) concentrations predict static and dynamic vascular properties.

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