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Serum receptor activator of nuclear factor-κ B ligand and osteoprotegrin are mediated to vascular calcification in the general population. Our knowledge is very sparse in hemodialysis and renal transplant patients. Receptor activator of nuclear factor-κ B ligand, osteoprotegrin, intact parathyroid hormone, calcium, and phosphorus were measured in blood samples of 45 hemodialysis and 45 age-matched renal transplant patients. Osteoprotegrin (P = 0.001) and intact parathyroid hormone (P = 0.001) levels in the hemodialysis patients were higher than the renal transplant recipients. Osteoprotegrin had positive correlation with duration of dialysis and age in the hemodialysis (r = 0.88, P = 0.001 and r = 0.34, P = 0.02, respectively) and renal transplant patients (r = 0.92, P = 0.001 and r = 0.46, P = 0.001, respectively). Hemodialysis patients have higher osteoprotegrin levels than the renal transplant recipients. It may act as a protective factor for renal osteodystrophy or only as a secondary phenomenon of advanced renal failure.

Objective The aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factors for vascular calcification and inflammation in hemodialysis (HD) and renal transplant (RT) patients. Method Serum was obtained from 45 stable chronic HD patients and 44 stable RT recipients. Biochemical factors, intact Parathormone, high-sensitive C-reactive protein (hsCRP), Fetuin-A and PTX3 levels were determined by standard methods. Results In the RT recipients PTX3 level was significantly higher than the HD patients [5.78(1.09–20.36) ng/mL vs. 1.65(0.24–7.89) ng/mL, p ≤ 0.001]. Serum Fetuin-A concentration was significantly higher in the HD compared to RT group [43.39(27.75–81.48) ng/mL vs. 38.76(22.26–89.07) ng/mL, p = 0.020]. hsCRP level was also higher in the HD than the RT group [2.90(0.1–8.50) mg/L vs. 1.1(0.1–7.9) mg/L, p = 0.003]. Conclusion Although our study shows that serum PTX3 is increased and Fetuin-A is decreased after successful RT, their direct role on atherosclerosis needs further studies in the future.

PURPOSE Disequilibrium between oxidative stress and antioxidant levels has been proposed as an important case of exudative age-related macular degeneration (AMD). The aim of the present study was to investigate homocysteine (Hcy) level and antioxidant paraoxonase 1 (PON1) activity within its phenotypes together with oxidized low-density lipoprotein (OX-LDL) levels in the patients with exudative AMD. METHODS Serum PON1 activity and plasma Hcy and OX-LDL levels were analyzed in 45 exudative AMD patients and compared with 45 healthy controls. Paraoxonase 1 activity was measured in serum using paraoxon and phenylacetate as substrates. The PON1 phenotype was determined using double-substrate method. Homocysteine and OX-LDL levels were determined by enzyme-linked immunosorbent assay method. RESULTS The distribution of PON1 phenotypes was significantly different between the patients with exudative AMD and control subjects (chi-square = 6.17, P = 0.01). AA phenotype with low activity was significantly more frequent in exudative AMD patients compared with healthy subjects (62.2% vs. 35.6%, respectively). Other phenotype frequencies in the patients compared with controls were as AB phenotype (intermediate activity) 28.9% versus 46.7% and BB phenotype (high activity) 8.9% versus 17.8%, respectively. Except in BB phenotype (P = 0.2), patients with AA and AB phenotypes had higher plasma Hcy levels in comparison to those of controls (P = 0.02 and P = 0.03, respectively). The mean OX-LDL levels, in all 3 phenotypes (P < 0.05), and OX-LDL/high-density lipoprotein ratio, in AA and AB phenotypes (P = 0.001, P = 0.1, respectively) but not in BB (P = 0.1), were significantly higher in the patients than controls. No significant differences in comparison of Hcy and OX-LDL levels between 3 PON1 phenotypes in both control (P = 0.6 for Hcy, P = 0.7 for OX-LDL) and patients (P = 0.8 for Hcy, P = 0.6 for OX-LDL) were found CONCLUSION Increased plasma OX-LDL levels and ratios of OX-LDL/high-density lipoprotein, as biomarkers of lipoprotein oxidative stress, higher levels of Hcy, as oxidant agent, and more common low or intermediate PON1 activity in patients with exudative AMD, compared with controls, indicate that PON1 activity is insufficient to explain the increased oxidative stress observed in exudative AMD.

Please cite this paper as: Tavana et al. (2011) Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00290.x. Background Sarcoidosis is an inflammatory, granulomatous disorder of unknown etiology. The role of cellular and humoral immune systems in this disease is unclear, whereas dysregulation of the immune system is suggested. Patients with sarcoidosis show diverse responses while exposed to various antigens. Although influenza vaccination is recommended in pulmonary sarcoidosis, its efficacy and safety has not been investigated. Objectives To evaluate safety and immunogenicity of influenza vaccine in patients with sarcoidosis. Patients/Methods Influenza vaccination was performed in 23 eligible patients with sarcoidosis (SP) and 26 healthy controls (HC). Antibody titers against H1N1, H3N2, and B influenza virus antigens were evaluated just before and 1 month after vaccination. Patients were followed for 6 months to assess vaccine safety. Results Serological response and magnitude of changes in antibody titers against influenza vaccine antigens were comparable between SPs and HCs. Women showed a better serological response against B antigen (P = 0·034) than men. Twenty-four-hour urine calcium was associated with antibody response against H1N1 [correlation coefficient (CC) = 0·477, P = 0·003] and H3N2 (CC = 0·352, P = 0·028) antigens. Serum angiotensin-converting enzyme correlated negatively with antibody response against B antigen (CC = −0·331, P = 0·040). Higher residual volume was associated with fewer rises in antibody titer against H3N2 antigen (CC = −0·377, P = 0·035). No major adverse events or disease flare-up was observed during follow-up. Conclusions In this study, influenza vaccination did not cause any major adverse event in SPs, and their serological response was equal to HCs. Studies with larger sample size and a broader selection of subjects could help validate the results of this study.

Objectives: To investigate the effect of lovastatin therapy and withdrawal on paraoxonase 1 (PON1) and arylesterase (ARE) activities, and low-density lipoprotein cholesterol (LDL-C) susceptibility to oxidation in people with type 2 diabetic nephropathy (T2DN). Design and methods: Lovastatin (20 mg/day) was administered to 30 people with T2DN for 90 days and then withdrawn for 30 days. PON1 and ARE activities were measured by the spectrophotometric method. Susceptibility of LDL-C to oxidation was determined as the production of conjugated dienes. Results: After 90 days of lovastatin intervention, PON1 and ARE activities and LDL-C lag phase were significantly increased (p = 0.004, 0.002, and

OBJECTIVE: The objectives of this study were to determine the effects of zinc supplementation on dietary intake, symptoms of eating problems, and serum zinc levels in hemodialysis patients. METHODS: Thirty-nine patients who received chronic maintenance hemodialysis were randomized to experimental (n 21) and placebo (n 18) groups given a daily supplement of 100 mg elemental zinc and corn starch, respectively, for 60 days. Dietary intake, body composition, and eating problems were assessed using 2-day dietary records, bioelectric impedance tests, and a questionnaire, respectively. Serum zinc levels were determined by atomic absorption before and after intervention. RESULTS: The mean daily macro- and micronutrients intakes and percentage of body fat in the supplemented group increased insignifi cantly. Administration of zinc improved appetite loss, dry mouth, nausea, and hypogeusia, while incidence of these symptoms increased in control group. A signifi cant increase (p 0.01) was observed in the mean serum zinc levels in the experimental group (102 4 vs. 76 3 g/dL) while changes in the placebo group were not signifi cant. CONCLUSIONS: Despite observed improvement in symptoms of eating problems and serum zinc levels in the supplemented group, more study over a longer period must be carried out to achieve clearer results.

Due to the association of oxidative stress and telomere shortening, it was aimed in the present study to investigate the possibility whether cyclosporine-A exerts its nephrotoxic side effects via induction of oxidative stress-induced renal telomere shortening and senescent phenotype in renal tissues of rats. Renal oxidative stress markers, 8-hydroxydeoxyguanosine, malondialdehyde, and protein carbonyl groups were measured by standard methods. Telomere length and telomerase activity were also evaluated in kidney tissue samples. Results showed that cyclosporine-A treatment significantly (P < 0.05) enhanced renal malondialdehyde, 8-hydroxydeoxyguanosine, and protein carbonyl groups levels, decreased renal telomere length, and deteriorated renal function compared with the controls. Renal telomerase activity was not affected by cyclosporine-A. Renal telomere length could be considered as an important parameter of both oxidative stress and kidney function. Telomere shortening and accelerated kidney aging may be caused by cyclosporine-induced oxidative stress, indicating the potential mechanism of cyclosporine-induced nephrotoxicity.

Objective Soluble receptor activator of nuclear factor-kappa B ligand (sRANKL) to osteoprotegerin ratio is designated as a bone metabolism equation in many rheumatologic disorders and would be modified with fish oil (FO) supplementation. Design and methods Eighty-three females with rheumatoid arthritis were divided randomly to 40 and 43 patients treated with (1 g/day) or without FO for 3 months accompanied with conventional drugs, respectively. Osteoprotegerin, sRANKL, tumor necrosis factor alpha (TNFα) serum levels were measured before and after treatment. Results Serum levels of osteoprotegerin increased, although sRANKL, TNFα and sRANKL/osteoprotegerin ratio decreased with FO therapy. A significant positive correlation was observed between sRANKL/osteoprotegerin ratio and TNFα levels ( r = 0.327 , p = 0.040) in the FO-treated group. Conclusions FO could decrease the inflammatory response by lowering of serum TNFα levels and sRANKL/osteoprotegerin ratio.

Background: Age-related macular degeneration (AMD) is the most common cause of elderly irreversible vision loss in the world. Since C-reactive protein (CRP) is a potential risk factor that has been known to induce AMD, this study was designed to explore the relationship between AMD and serum levels of high sensitivity C-reactive protein (hsCRP), and endothelin-1 (ET-1). Methods The subjects were 48 males with AMD (28 with wet type and 20 with dry type) having a mean age of 69.4 ± 9.6 years and a matched group of 45 apparently healthy control subjects. The AMD was diagnosed using a slit-lamp with super filled lens, fundus photography and fluorescein angiography. Levels of hsCRP and ET-1 were determined using ELISA methods. Results: hsCRP (6.96 ± 5.15 vs. 3.64 ± 4.67 mg/l, P

Purpose: To evaluate the effects of onion juice on sodium-selenite induced cataract formation. Materials and Methods: Thirty-two 10-day-old Wistar-albino rat pups were divided into four equal groups. Group 1 received only subcutaneous saline injection. In Group 2, sodium-selenite (30 nmol / g body weight) was injected subcutaneously. In Group 3, subcutaneous sodium-selenite was injected and one drop 50% diluted fresh juice of crude onion was instilled every 8 h into the right eye for 14 days; the left eye received no treatment. Group 4 rats were similar to those of Group 3, the only difference being that of undiluted fresh juice of crude onion. The development of cataract was assessed. Rat lenses were analyzed for total antioxidant (TA) level, and for activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD). Results: Both eyes of all rats in Group 1 did not exhibit cataract formation . In Group 2, all rats developed Grade 3 cataract in the lenses of both eyes. The difference in exhibited cataract in the lens of the right eyes in all rats between Group 2 and any eyes of groups 3 or 4 were significant ( P = 0.001). The mean TA level and mean activities of SOD and GPX in Group 2 rat lenses were significantly lower than the values in lenses of all rats in Group 1 ( P = 0.001, 0.003, 0.001), and in the lenses of the right eyes of rats in Groups 3 and 4 ( P = 0.001, 0.020, 0.001). Conclusion: Instillation of onion juice into the rat eyes can effectively prevent selenite-induced cataract formation. This effect was associated with increased TA level, SOD and GPX activities in the lens.

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.

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.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 Por = .05 was considered significant.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).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.

Aims: We aimed to assess humoral immune response to the influenza vaccine in adult kidney transplant recipients (KTRs) subjected to two immunosuppressive regimens containing either mycophenolate mofetil (MMF) or azathioprine (Aza). Methods: 40 eligible KTRs (24 treated with Aza [KTRs-Aza] and 16 treated with MMF [KTRs-MMF]) and 40 matched healthy controls (HCs) were administered the trivalent 2006–2007 anti-influenza vaccine. Antibody (Ab) titers were measured before (pre-vacc) and 1 month after (post-vacc) vaccination. The proportion of protective Ab titers (i.e. ≧1:40), the serological response (i.e. ≧4-fold rise in titers) rates, and the magnitudes of change in titers were evaluated. Results: KTRs and HCs were similar in serologic responses, magnitudes of change in Ab titers, and proportions of acquired protective titers against all antigens. Whereas KTRs-MMF and KTRs-Aza were identical in magnitude of rise in titers as well as in serologic responses, KTRs-MMF did poorer in developing post-vacc-protective titers against A/H1N1 (p < 0.05). The function of the transplanted kidney has not deteriorated after vaccination. Conclusions: Anti-influenza vaccination was safe in KTRs and evoked Ab responses comparable to those of HCs. KTRs-MMF and KTRs-Aza responded almost equally to the vaccine. Annual anti-influenza vaccination can be recommended to all stable KTRs.

Objectives. Vascular complications are common after renal transplantation. In this study we correlated Doppler sonographic indices and transplant kidney function. Methods. We reviewed data on 244 renal transplant patients. Doppler ultrasonographic evaluation was performed during the first 2 weeks after renal transplantation. We determined resistive index (RI) and pulsatility index (PI) in the interlobar arteries and thrombosis of renal and lower limb veins. Serum creatinine (Cr) and cyclosporine levels were evaluated prior to sonographic assessment. Results. The mean age of the 142 male and 102 female patients was 36.31 ± 3.30 years. Prevalence of real artery stenosis was 9.5%. In these patients the mean serum Cr level (2.21 ± 1.83 mg/dL) was significantly higher than among patients with patent renovascular tributary (1.49 ± 1.00 mg/dL; P = .03). RI and PI were also significantly correlated with serum Cr(P = .05 and .001, respectively). There was no relationship between cyclosporine level or panel-reactive antibody with RI and PI. Retransplant patients showed higher RI than first renal allograft recipients (0.72 ± 0.16 vs 0.63 ± 0.11; P = .006). Serum Cr level was higher among renal allograft recipients with Doppler evidence of thrombosis of the lower limb veins (3.1 ± 0.98 mg/dL versus 1.56 ± 1.13 mg/dL; P = .04). Conclusions. RI and PI are two valuable Doppler ultrasonographic markers to determine renal allograft function and related vascular complications.

Disturbances in metabolism of lipo-proteins and oxidative modification of low-density lipoprotein contribute to cardiovascular disease and development of oxidative stress in patients under renal replacement therapy (hemodialysis and renal transplant). This study was designed to compare oxidized low-density lipoprotein levels and lipid profiles in renal transplant recipients and hemo-dialysis patients.We investigated the concentration of oxidized low-density lipoprotein in hemodialysis (n = 38) and renal transplant (n = 59) patients who had no active inflammatory disease, liver disease, or malignancy, and results were compared to a control group (n = 30).Renal transplant recipients had hypercholesterolemia, hypertriglyceridemia, and increased oxidized low-density lipoprotein levels (P = .019) compared with the control group. Hemodialysis patients had moderate hypertriglyceridemia (not significant), hypercholesterolemia, decrease in high-density lipoprotein, and increase in oxidized low-density lipoprotein levels (P.0001) compared with the control group. In the renal transplant group, oxidized low-density lipoprotein level had a negative correlation with the duration after transplant (r = -0.407; P = .026), positive association with cyclosporine level (r = 0.288; P = .04), and negative correlation with high-density lipoprotein level (r = -.30; P = .05); oxidized low-density lipo-protein/high-density lipoprotein ratio also had a positive correlation with cyclosporine level (r = 0.309; P = .027) and negative correlation with high-density lipoprotein level (r = -0.72; P.001) in the renal transplant group and high-density lipoprotein in the hemodialysis group (r = -0.87; P.001). Multiple stepwise regression analyses showed that oxidized low-density lipoprotein only was associated with cyclosporine level (R2 = 0.155; β=0.393; P = .024).History of cardiovascular disease is the most important factor associated with end-stage renal disease, and high oxidized low-density lipoprotein level, oxidized low-density lipo-protein/high-density lipoprotein ratio, and high-density lipoprotein level may affect cardiovascular disease.

To explore the probable association of serum hepcidin and haemoglobin levels with iron and inflammation statuses in patients of chronic kidney disease stage 4 with anaemia.The cross-sectional study was conducted at Tabriz University of Medical Sciences, Iran, from March 2011 to October 2012, and comprised patients of chronic kidney disease stage 4 with anaemia. Serum biochemical factors as well as hepcidin, ferritin, interleukin 6, high sensitivity C-reactive protein and iron levels were measured using standard methods. Statistical correlations were established using regression analysis and Pearson's correlation coefficient.There were 40 patients among whom 15(37.5%) were males and 25(62.5%) were females with an overall mean age of 55.68±14.4 years. There was a significant inverse relationship between hepcidin and haemoglobin levels (p0.05). There were significant correlations between hepcidin with iron status, nutritional and inflammatory markers such as ferritin, Total iron binding capacity, albumin and interleukin 6 (p0.05 each).Hepcidin had negative correlation with haemoglobin level in stage 4 chronic kidney disease patients with adequate iron stores, which could be effective in the development of anaemia in such patients.

Aims: Following carnitine administration a decrease in plasma levels of triglyceride (TG) and increase in total high-density lipoprotein cholesterol (HDL-C) has been reported. Our hypothesis was that it also improves the HDL2/HDL3 ratio, symptomatic intradialytic hypotension, and anemia in hemodialysis (HD) patients. Methods: Forty HD patients with a mean (± SD) age of 53 ± 13 years were treated with 500 mg/day carnitine taken orally for 2 months. Patients were used as their own controls (before treatment). Lipid and lipoproteins were determined by Alcyon Abbott autoanalyzer. HDL subclasses were measured by magnesium precipitation after fractionation with dextran sulfate. Hemoglobin, hematocrit and serum albumin were measured by standard methods. The results were analyzed by SPSS 11.05. Results: We found a significant decrease in serum TG (2.22 ± 0.99 vs. 1.93 ± 1.07 mmol/l, p < 0.01) and VLDL-C (0.93 ± 0.36 vs. 0.81 ± 0.34 mmol/l, p = 0.01) and a marked increase in HDL-C (0.9 ± 0.16 vs. 1.06 ± 0.24 mmol/l, p < 0.05), HDL2-C (0.17 ± 0.06 vs. 0.27 ± 0.14 mmol/l, p < 0.05) and albumin (37 ± 4 vs. 42 ± 5 g/l, p = 0.01) levels. The serum levels of total cholesterol (4.61 ± 0.89 vs. 4.5 ± 0.95 mmol/l, p = 0.1), LDL-C (2.78 ± 0.85 vs. 2.6 ± 0.89 mmol/l, p > 0.05), HDL3-C (0.73 ± 0.1 vs. 0.79 ± 0.17 mmol/l, p > 0.05), hemoglobin, hematocrit, and intradialytic blood pressure did not change after the treatment. Conclusion: Treatment with 500 mg/day carnitine taken orally for 2 months reduces serum levels of TG and VLDL-C, and increases HDL-C, HDL2-C and albumin in HD patients.

Background High serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD. Methods CKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods. Results Serum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P

Background aims Chronic kidney disease (CKD) attributed to cisplatin is well documented. Mesenchymal stromal cells (MSCs) are proven to be renotropic. Although they have been shown to improve function in CKD and reduce fibrosis in different experimental rodent models, their efficiency in primates is unknown. The present study aimed to evaluate the prevention of CKD and reduction of fibrosis in monkeys treated with MSCs after cisplatin nephrotoxicity. Methods We induced CKD in adult rhesus Macaca mulatta monkeys by means of intravenous administration of cisplatin. Autologous MSCs were transplanted by means of intrarenal arterial injections to assess the adverse effects of cisplatin in two CKD models: preventative and stable. Preventative CKD monkeys ( n = 3) underwent cell transplantation 4 days after the cisplatin injection. The stable CKD monkeys ( n = 2) underwent cell transplantation 6 months after the cisplatin injection. Non-treated ( n = 4) and normal saline–injected animals ( n = 3) comprised the control and vehicle groups, respectively. We followed the animals for survival rate, serum biochemistry, urine analysis and histopathological indices. Results In the preventive CKD model, MSC transplantation tended to improve some renal functions but significantly reduced the histopathologic score compared with the vehicle and control groups. In the stable CKD model, MSCs did not ameliorate renal function or pathological score. Conclusions These results suggest that MSCs tend to delay progression of CKD and fibrosis but do not reduce established interstitial fibrosis in this unique primate model of cisplatin-induced nephrotoxicity.

Background: Endotheline-1 (ET-1), an endothelial mediator, influences on mineral metabolism; especially vascular calcification in uremic patients. Objectives: The aim of the present study was to evaluate of ET-1, high-sensitivity C-reactive protein (hs-CRP) and mineral metabolites as the main factors for vascular calcification and inflammation in hemodialysis (HD) patients. Patients and Methods: In this cross-sectional study, 46 chronic stable HD patients were selected from nephrology departments of Tabriz University of Medical Sciences affiliated hospitals and classified based on phosphorus (P), Ca-P product (Ca × P) and intact Parathyroid Hormone (iPTH) levels. We evaluated fasting serum ET-1and hs-CRP levels by the standard methods and compared with 46 healthy control subjects. Results: The levels of serum hs-CRP and ET-1 were significantly higher in the patient’s group compared with controls (4.40 ± 1.26 vs. 1.38 ± 1.61, P < 0.0001, and 2.31 ± 0.87 vs. 0.75 ± 0.48, P < 0.0001, respectively) and with regard to Ca × P product cut-off point (3.99 ± 0.78 vs. 5.33 ± 1.64, P < 0.0001, and 2 ± 0.73 vs. 3.04 ± 0.73, P < 0.0001 respectively). ET-1 was correlated significantly with hs-CRP level (r = 0.776, P < 0.0001). Serum P, Ca × P and iPTH levels directly and Ca indirectly were correlated with serum ET-1 in HD patients (r = 0.932, P < 0.0001, r = 0.766, P < 0.0001, r = 0.514, P < 0.0001, r = -0.538, P < 0.0001 respectively). Multiple regression analysis demonstrated that serum P were independently associated with ET-1 levels (β = 0.932, P < 0.0001). Conclusions: Serum P and iPTH levels were independently associated with ET-1 and those may play a role in development of endothelial dysfunction in chronic kidney disease.

Plasma protein growth arrest-specific 6 (GAS6) and matrix Gla protein (MGP) are crucial mediators of vascular calcification and are involved in the development of vascular complications in chronic kidney diseases. This study was set out to investigate the relationship between plasma GAS6 levels and MGP in patients with end-stage renal disease on maintenance hemodialysis.Forty-six hemodialysis and 46 healthy individuals with normal kidneys were recruited. Plasma GAS6 and MGP concentrations and related biochemical factors were quantified as well as collection of data on clinical characteristics.Plasma GAS6 levels were significantly higher in the hemodialysis patients as compared with the control group (763.52 ± 187.91 pg/mL versus 421.63 ± 189.91 pg/mL, P.001). Plasma MGP concentration was significantly lower in the hemodialysis patients than the control group (52.35 ± 12.35 ng/mL versus 6.60 ± 19.54 ng/mL, P.001). The levels of GAS6 were inversely associated with MGP (r = -0.341, P = .02) in the hemodialysis patients.Increased GAS6 and decreased MGP levels in hemodialysis patients, as mediators of induction or prevention of vascular calcification, and their inverse correlation may suggest that there might be a role in increased calcification process in hemodialysis patients or only as a secondary phenomenon of advanced kidney failure. Their direct role on vascular calcification needs further studies in the future.

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.

Low fetuin-A and 1,25-hydroxyvitamin D3 (vitamin D) levels accompanied with high intact parathyroid hormone (PTH) contents are associated with cardiovascular disease in dialysis patients. The aim of present study was to evaluate the relationship between vitamin D receptor (VDR) gene FokI and ApaI polymorphisms with serum levels of fetuin-A, vitamin D, and intact PTH in hemodialysis patients.Serum was obtained from 46 stable chronic hemodialysis patients and 43 healthy controls. Serum levels of intact PTH, fetuin-A, vitamin D, calcium, and phosphorus were measured. Genotyping of the VDR gene was performed using standard methods.Serum fetuin-A and vitamin D levels were significantly lower, whereas serum levels of PTH, calcium, and Phosphorus were higher in the hemodialysis patients than in the healthy controls. The FokI genotypes were more frequent in the hemodialysis patients than the control group (P = .004). With respect to FokI genotypes, intact PTH level was higher among the hemodialysis patients compared to the controls (P = .02). In contrast, vitamin D level was lower in the hemodialysis patients with ApaI genotypes compared to the control group (P = .04).Our study shows that increased serum level of PTH and decreased fetuin-A and vitamin D levels may increase susceptibility of atherosclerosis in patients with hemodialysis through VDR gene FokI and ApaI polymorphisms.

Project The aim of this study was to determine the effects of zinc supplementation on serum zinc and leptin levels as well as on anthropometric status and some biochemical parameters in hemodialysis (HD) patients. Procedure In this randomized, double-blind, and placebo-controlled trial, sixty HD patients were randomly divided into groups to receive a daily supplement of 100 mg elemental Zn (supplemented group) or placebo (control group) for 60 days. Anthropometric measurements were taken using standard calibrated instruments. Serum zinc and leptin levels were determined by atomic absorption and ELISA method respectively before and after intervention. Results Zinc supplementation resulted in significant increase in the mean serum zinc level in the experimental group while changes observed in the placebo group were not significant. The mean serum leptin in women part of the experimental group was decreased significantly after supplementation. After adjusting for age, BMI, body fat (%), serum zinc and dietary Zn intake, a negative and significant association was observed between serum zinc and leptin levels in all subjects (β = −0.33, P = 0.03) as a result of Zn supplementation. Conclusions More studies are needed to clarify the mechanisms by which serum leptin level is influenced as a result of zinc supplementation in HD patients.

Serum receptor activator of nuclear factor-κ B ligand and osteoprotegrin are mediated to vascular calcification in the general population. Our knowledge is very sparse in hemodialysis and renal transplant patients. Receptor activator of nuclear factor-κ B ligand, osteoprotegrin, intact parathyroid hormone, calcium, and phosphorus were measured in blood samples of 45 hemodialysis and 45 age-matched renal transplant patients. Osteoprotegrin (P = 0.001) and intact parathyroid hormone (P = 0.001) levels in the hemodialysis patients were higher than the renal transplant recipients. Osteoprotegrin had positive correlation with duration of dialysis and age in the hemodialysis (r = 0.88, P = 0.001 and r = 0.34, P = 0.02, respectively) and renal transplant patients (r = 0.92, P = 0.001 and r = 0.46, P = 0.001, respectively). Hemodialysis patients have higher osteoprotegrin levels than the renal transplant recipients. It may act as a protective factor for renal osteodystrophy or only as a secondary phenomenon of advanced renal failure.

Patients on maintenance hemodialysis (HD) face an increased risk of atherosclerosis, a crucial problem and the leading cause of cardiovascular morbidity and mortality. This study was designed to evaluate the effects of zinc supplementation on paraoxonase (PON) enzyme activity in patients on HD.This double-blind randomized controlled trial was conducted from June 2005 to June 2007. Sixty HD patients were enrolled and divided into two groups: treatment (case) and control. The treatment and control groups were treated with 100 mg/day zinc or placebo, respectively, for 2 months. Serum zinc concentration was measured by atomic absorption spectrophotometry. PON activity was evaluated by spectrophotometric method. Lipid profile was determined using commercial kits, and apolipoprotein AI (Apo-AI) and B (Apo-B) levels were measured by commercial immunoturbidimetric kits.In the case group, there was no significant change in the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and Apo-B levels, while the serum levels of high-density lipoprotein (HDL), Apo-AI, and PON activity were significantly increased (p = 0.02). In the control group, although significant increases were observed in the serum levels of TC, TG, and Apo-B (p = 0.009, 0.019, and 0.001, respectively), the serum PON activity was significantly decreased (p = 0.025) and the serum levels of HDL, LDL, and Apo-AI were not changed. At the end of intervention period, the serum level of Apo-AI and PON activity were significantly higher in the case group.Zinc supplementation increased both the activity of PON and the serum level of Apo-AI in the HD patients.

This study was conducted to determine the effect of fish oil (FO) supplements on high density lipoprotein cholesterol (HDL-C), apolipoprotein-AI (Apo-AI), malondialdehyde (MDA), arylesterase (Aryl), and paraoxonase-1 (PON1) activity in female patients with rheumatoid arthritis (RA).A total of 90 RA patients were randomly allocated into two groups that were treated with one FO pearl (1 gr) daily or placebo for three months in addition to conventional treatment. HDL-C, Apo-AI, and MDA levels as well as PON1 and Aryl activities were measured before and after treatment. Independent t-test was used to match basal parameters of case and control groups. Paired t-test was used to assess significance of the differences. Correlation was evaluated by Pearsons test and the statistical significance was set at P0.05.No significant differences were noted between FO and placebo patients with regards to age, disease duration, post-menopausal status, conventional therapy, body mass index (BMI), and numbers of swollen and tender joints at the beginning of the study. There were 83 patients who completed the three-month follow up. Serum levels of HDL-C (P = 0.018), Apo-AI (P = 0.165), Aryl (P = 0.026), and PON1 (P = 0.049) activity increased, whereas MDA levels decreased significantly with FO supplementation (P = 0.077). Significant correlations between increased PON1 activity and both HDL-C (P = 0.007, r = 0.419) and Apo-AI (P0.001, r = 0.742) concentrations as well as between HDL-C and Apo AI levels (P = 0.01, r = 0.403) were found.According to the results of this study, FO could increase serum HDL-C and PON1 levels and Aryl activity in female patients with RA.

Objectives This study was designed to determine the effects of zinc supplementation on oxidative stress in hemodialysis (HD) patients through evaluating total antioxidant capacity (TAC), whole blood glutathione peroxidase (GSH) level, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) level. Design and Setting Double-blinded randomized controlled trialfrom October 2006 to December 2007 at Tabriz Imam Khomeini Hospital. Subjects Sixty-five HD patients were randomly enrolled into 2 groups. Intervention Patients received placebo in group A and zinc (100 mg/day) in group B for 2 months. After a washout period for 2 months, the groups were crossed over and the study was continued for an additional 2 months. Main outcome measures Serum zinc concentration was measured using atomic absorption spectrophotometry. TAC, GSH level, and SOD activity were determined by commercial enzyme-linked immunosorbent assay kits. MDA level was measured using a thiobarbituric acid method. Results The levels of serum zinc, TAC, GSH ( P P P = .003 for group B) significantly increased after zinc supplementation whereas the serum level of MDA decreased after the same period ( P = .003 for group A and P Conclusions Zinc supplementation for 2 months improved the serum levels of zinc, antioxidant status, and lipid peroxidation in HD patients.

Please cite this paper as: Tavana et al. (2011) Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2011.00290.x. Background Sarcoidosis is an inflammatory, granulomatous disorder of unknown etiology. The role of cellular and humoral immune systems in this disease is unclear, whereas dysregulation of the immune system is suggested. Patients with sarcoidosis show diverse responses while exposed to various antigens. Although influenza vaccination is recommended in pulmonary sarcoidosis, its efficacy and safety has not been investigated. Objectives To evaluate safety and immunogenicity of influenza vaccine in patients with sarcoidosis. Patients/Methods Influenza vaccination was performed in 23 eligible patients with sarcoidosis (SP) and 26 healthy controls (HC). Antibody titers against H1N1, H3N2, and B influenza virus antigens were evaluated just before and 1 month after vaccination. Patients were followed for 6 months to assess vaccine safety. Results Serological response and magnitude of changes in antibody titers against influenza vaccine antigens were comparable between SPs and HCs. Women showed a better serological response against B antigen (P = 0·034) than men. Twenty‐four‐hour urine calcium was associated with antibody response against H1N1 [correlation coefficient (CC) = 0·477, P = 0·003] and H3N2 (CC = 0·352, P = 0·028) antigens. Serum angiotensin‐converting enzyme correlated negatively with antibody response against B antigen (CC = −0·331, P = 0·040). Higher residual volume was associated with fewer rises in antibody titer against H3N2 antigen (CC = −0·377, P = 0·035). No major adverse events or disease flare‐up was observed during follow‐up. Conclusions In this study, influenza vaccination did not cause any major adverse event in SPs, and their serological response was equal to HCs. Studies with larger sample size and a broader selection of subjects could help validate the results of this study.

Objectives Tuberculosis remains one of the most common infectious diseases and a leading cause of mortality world wide. There is some evidence for the possible involvement of Mycobacterium tuberculosis in atherosclerosis. We aim to investigate total antioxidant capacity (TAC), red blood cell superoxide dismutase (SOD) activity, whole blood glutathione peroxidase (GPX) activity, low-density lipoprotein (LDL) susceptibility to oxidation, and malondialdehyde (MDA) levels in patients with pulmonary tuberculosis (PTB). Methods Forty-five males with active PTB (case group) and 45 healthy age-matched males (control group) were enrolled in the study. TAC, SOD and GPX activities were determined by commercial ELISA kits. MDA levels were measured using the thiobarbituric acid method. LDL susceptibility to oxidation was assessed by measuring lag phase duration. Results TAC, SOD and GPX activities, and lag phase duration in the case group were significantly lower than the control group ( p = .002, p = .004, p = .008, and p = .004, respectively; independent), while the MDA levels was higher in case group ( p = .024). Conclusions Our findings suggest a higher susceptibility of LDL to oxidation and higher levels of lipid peroxidation, and therefore, a possible higher risk of atherosclerosis in patients with PTB.

INTRODUCTION. This study was designed to determine the protective effect of red grape seed extract (RGSE) on gentamicin-induced nephrotoxicity in rats. MATERIALS AND METHODS. Thirty male Wistar rats were divided into 3 groups to receive RGSE, for 60 days followed by intraperitoneal injection of saline solution (as placebo) for 8 days (group 1); RGSE followed by gentamicin for 8 days (group 2); and gentamicin without pre-medication of RGSE (group 3). Oral RGSE, 40 mg/kg/d, and intraperitoneal injection of gentamicin, 100 mg/kg/d, were administered in these groups of rats. Blood and urine samples were collected on days 0 and 68 of the study. Then, the kidneys were removed for pathologic examination. RESULTS. On day 68, serum creatinine and blood urea nitrogen concentrations were highest in group 3, which was significantly higher than in group 1 (P = .001 and P = .004, respectively), while slightly higher than in group 2 (P = .30 and P = .50, respectively). Fractional excretion of sodium was not significantly different between the three groups. Histopathological evaluation showed that rats in group 3 had significantly higher degrees of severe acute tubular necrosis and interstitial mononuclear cell infiltration than the rats in groups 1 and 2 (P.001). CONCLUSIONS. This animal study suggests that pretreatment with RGSE protects against gentamicin-induced acute kidney injury as evident on tissue histology. However, this was not accompanied with significant improvement in biochemical markers of kidney injury.

PDpoietin is a recombinant erythropoietin alfa that has been introduced by a manufacturer in Iran. We assessed the effectiveness and complications of PDpoietin in comparison with Eprex in anemic patients on hemodialysis.This clinical trial was performed in a multicenter setting. Patients with a hemoglobin level less than 12 g/dL were assigned into 2 groups in order to receive either Eprex (Janssen Cilag) or PDpoietin (Pooyesh Darou) for 3 months.Forty-one and 34 patients completed the study in the PDpoietin and Eprex groups, respectively. The mean hemoglobin levels at baseline were not significantly different between the two groups of patients with PDpoietin and Eprex. In both groups, hemoglobin levels increased significantly, but there were no significant differences between the two groups at months 1, 2, and 3. At the end of the study, the mean hemoglobin levels reached 11.6 +/- 1.7 g/dL and 11.8 +/- 1.9 g/dL, respectively (P = .002; P = .01). The mean hemoglobin per cumulative of drug dose index (hemoglobin/[erythropoietin dose/1000 x injections per month]) was not significantly different between the two groups at different treatment stages, and it did not change significantly in each group during the course of the study. No serious complications were reported.Eprex and PDpoietin could equally increase the hemoglobin levels with no significant complication. Therefore, PD can be used for treatment of anemia in patients on dialysis, and the patients will have the advantages of its availability and low price.

We aimed to evaluate the high-sensitivity C-reactive protein (HS-CRP) level changes at the beginning and after withdrawal of lovastatin therapy in patients with diabetic nephropathy.Thirty male patients with type 2 diabetes mellitus and diabetic nephropathy were enrolled in the study. Lovastatin, 20 mg/d, was administered for 90 days. Afterwards, Lovastatin was withdrawn for the next 30 days. Blood samples were obtained before the intervention, on the 90th day, and days 1, 7, and 30 after withdrawal of Lovastatin. Serum level of HS-CRP was determined by enzyme-linked immunosorbent assay. Alterations in lipid profile was assessed, as well, and compared with that of HS-CRP.Serum level of HS-CRP was significantly reduced after 90 days of lovastatin therapy (P.001). Then, the HS-CRP reached the pretreatment baseline level on the 7th day after lovastatin withdrawal and maintained until the 30th day (P.001). Serum HS-CRP changes showed no significant association with lipid profile except for serum total cholesterol level (r = 0.9, P = .006) after 3 months of lovastatin therapy. Their association was re-evaluated after 7 days and 1 month of treatment withdrawal and no significant correlations were found.Our findings suggest that lovastatin decreases serum CRP level in patients with diabetic nephropathy, and 7 days after lovastatin cessation, CRP level increases again.

Instruction. We investigated the correlation between atherosclerosis and tissue and serum levels of endothelin-1 in patients with chronic kidney disease (CKD). MATERIALS AND METHODS. Arterial samples were obtained from 35 patients with CKD during arteriovenous fistula placement. Thirty-one patients with cardiovascular disease who underwent coronary artery bypass graft (CABG) were selected as the atherosclerotic group, and a piece of their aorta punched during CABG was obtained. Also, a small piece of the renal artery was dissected during donation in 24 kidney donors (control group). Tissue endothelin-1 level was measured and atherosclerosis grading was determined by pathologic examination. Serum levels of endothelin-1 were also measured in the three groups. Results. The mean tissue endothelin-1 levels were 10.73+/-7.57 pg/mL, 12.16 +/- 3.95 pg/mL, and 0.93 +/- 1.06 pg/mL in the patients with CKD, those with CABG, and donors, respectively (P.001). The mean serum endothelin-1 level was 25.23 +/- 15.15 pg/mL in the patients with CKD, 21.13 +/- 17.22 pg/mL in the patients with CABG, and 2.66 +/- 1.51 pg/mL in the donors (P.001). Atherosclerosis grades correlated with tissue endothelin-1 level (r = 0.823, P.001) and serum endothelin-1 level (r = 0.608, P.001) in the patients with CKD. Multiple regression analysis showed tissue endothelin-1 level as the main predicting factor of atherosclerosis (P.001). CONCLUSIONS. Tissue endothelin-1 concentration is more important than serum endothelin-1 or lipids levels in prediction of atherosclerosis. Thus, blockade of tissue endothelin-1 receptors with its antagonists may prevent atherosclerosis progression.

Doppler ultrasonography (DU) is mostly used for assessment of both graft and native kidneys' vascular status. In this study, correlation between the DU indexes and kidney allograft function was evaluated.Hospital records of 273 kidney transplant patients (154 men and 119 women) were reviewed. In all cases, DU had been performed 1 month after kidney transplantation. We evaluated the data on the resistive index (RI) and pulsatility index (PI) in the interlobar arteries and renal artery stenosis (RAS), and renal vessels thrombosis were determined. Concurrent serum creatinine and cyclosporine values were assessed in relation to the DU findings.The RI and PI had significant linear correlations with serum creatinine (P = .03 and P = .002, respectively). Also, there were direct linear correlations between the age of the patients and the RI and PI values. The frequency of RAS was 10.3%. In patients with RAS, the mean creatinine level (2.08 +/- 1.70 mg/dL) was significantly higher than that in patients without RAS (1.48 +/- 0.97 mg/dL; P = .004). Despite this finding, RI and PI were significantly lower in patients with RAS than in the patients with patent renovascular tributary (0.59 +/- 0.15 versus 0.65 +/- 0.11; P = .03 and 1.02 +/- 0.40 versus 1.18 +/- 0.46; P = .049, respectively). There were no associations between serum cyclosporine level or panel reactive antibodies and the RI or PI.The RI and PI are valuable DU markers for determining the kidney allograft function and the related vascular complications.

Objectives Doppler ultrasonography is mostly used for assessment of both graft and native kidney vascular status. In this study, correlation between Doppler sonographic indices and transplanted kidney function was evaluated. Methods In our retrospective study, we reviewed data on 273 renal transplanted (RTx) patients. The Doppler ultrasonographic evaluation included resistive index (RI), pulsatility index (PI) in interlobar arteries as well as stenosis (TRAS) or thrombosis of renal arteries and veins. Serum creatinine (Cr) and cyclosporine levels (CsA) were measured just prior to sonography. Results The mean age of 154 male and 119 female patients was 36.67 ± 13.13 years. Both RI and PI showed significant linear correlations with serum Cr ( P = .033 and P = .002, respectively). Also, direct linear correlations existed between patient age and RI and PI values ( P = .004; r = +.174 and P = .003; r = +.183 respectively). The prevalence of TRAS was 11.35%. Among patients with TRAS or thrombosis the mean Cr level (2.08 ± 1.7 mg/dL) was significantly higher than that among patients without TRAS or thrombosis (1.48 ± 0.97 mg/dL; P = .004). Despite this finding, RI and PI were significantly lower among patients with TRAS or thrombosis than those with a patent renovascular tributary (0.59 ± 0.15 vs 0.65 ± 0.11; P = .029 vs 1.02 ± 0.40 vs 1.18 ± 0.46; P = .049). Conclusions Both RI and PI were two valuable Doppler ultrasonographic markers to evaluate renal allograft function and related vascular complications.

To analyze the role of 3 polymorphisms of the renin-angiotensin system (RAS) in renal transplant recipients (RTRs) and correlate them with graft function.The present study was performed in the Drug Applied Research Center, Tabriz Medical University, Tabriz, Iran from September 2003 to December 2005 on 108 RTRs (66 males and 42 females, with a mean age of 37.34 +/- 4.97 years) with stable allograft function (creatinineor =2.2 mg/dl). Following the DNA extraction from the blood leukocytes, the genotypes of the angiotensin converting enzyme (ACE I/D), angiotensinogen (ANG M235T), and angiotensin II type 1 receptor (ATR1 A1166C) were determined by polymerase chain reaction. The magnitude of clearance of creatinine (ClCr) in the setting of each of the above RAS polymorphisms was determined. The ClCr was measured by modification of diet in renal disease formula. Values were expressed as mean +/- SD; por =0.05 was considered to indicate statistical significance.There was no association of each genotype of the RAS alone with ClCr, serum urea, cyclosporine through level and the degree of urinary protein excretion rate. However, patients with the DD genotype of angiotensin converting enzyme + CC genotype of angiotensin II type I receptor polymorphisms had lower ClCr (p=0.05) and a higher urinary protein excretion rate (p=0.03). Other combination genotypes of RAS had no effect on allograft function. Interestingly, the percent of hypertensive patients in the C allele (70%) was more than the A allele (30%) of ATR1 polymorphism (p=0.04).Although none of the single gene polymorphisms of the RAS affected renal allograft function, combinations of these genotypes were associated with the outcome of allograft function.

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.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.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).Although cyclosporine-induced nephrotoxicity is not completely eliminated by isoproterenol, the latter showed some protective effects.

Objectives. Alloreactive T cells recognize antigens via direct and indirect pathways. The competency of costimulatory molecules on antigen-presenting cells (APC) is important. An active form of vitamin D (1,25(OH) 2 D 3 , calcitriol) inhibits APC cell maturation and expression of costimulatory molecules. Herein we studied the immunosuppressive effects of calcitriol, which was started in the donors and continued in the kidney recipients. Methods. In this prospective study, candidates for living donor renal transplantation were randomly assigned into two groups: the treatment group were prescribed calcitriol (0.5 μg/day) started in the donor 6 days before donation and continued in recipient side for 6 months after transplantation. The control group received the conventional immunosuppressive regimen, namely, cyclosporine/mycophenolate mofetil and prednisolone. In each group, a recipient blood sample was obtained before and 6 months after transplantation. Diagnostic study of the T-cell markers-CD3, CD4, and CD25-were performed with a flow cytometery technique. Results. The mean values of CD3 + CD4 + CD25 + T cells in the treatment group (four women and five men; 40.8 ± 8.5 years) and the control group (four women and six men; 37.2 ± 10 years) were at 14.2 ± 4.2% and 15.4 ± 4.5% of total peripheral lymphocytes. Six months after transplantation, these percentages increased to 29 ± 6.3% in the treatment group and decreased to 12.1 ± 4.5% in the controls (P

This study sought to evaluate the bioequivalence of Iminoral (test) versus Neoral (reference) in healthy volunteers, as well as safety and efficacy of Iminoral treatment in renal transplant recipients following conversion from Neoral. Methods After an overnight fast, 18 healthy volunteers received the assigned treatment (test or reference, 200 mg single dose) in a cross-over fashion with a washout period of 14 days. The blood samples were drawn at various times after drug administration. Cyclosporine blood concentration was measured by high-performance liquid chromatography using an ultraviolet detector. In the second phase of study, stable renal transplant patients who were on Neoral were enrolled in the study in an open-label manner. They were converted from Neoral to Iminoral based on a 1:1 dose equivalence. Cyclosporine trough levels and changes in serum creatinine, lipid profile, electrolytes, and uric acid were measured before and periodically after conversion for 6 months. Results The 90% confidence interval of the test/reference ratio was within the acceptable limits of 0.8 to 1.25. Relative bioavailability of Iminoral in healthy subjects was 99.0%. There was no significant difference in cyclosporine concentrations and serum creatinines following conversion to Iminoral in renal transplant patients ( n = 41). There were no reports of major toxicity or of graft rejection and no need for dose adjustment related to Iminoral. Conclusions Single doses of Neoral and Iminoral are bioequivalent in healthy subjects. Renal transplant recipients maintained on Neoral can be safely and effectively converted to Iminoral on a 1:1 conversion ratio.

In this study the effect of losartan and enalapril on the reduction of DNA damage was evaluated in regard to renin-angiotensin system (RAS) polymorphisms.After determination of genotypes of RAS polymorphism by PCR, 64 renal transplant recipients were randomly allocated to one of four groups: the first and second groups were treated with E (E+: 10 mg/day) and L (L+: 50 mg/day) alone, respectively. The third group received E+L (E+L+: 10 + 50 mg/day), and the forth group received no medication (E-L-). The subjects were followed for 8 weeks. After a 2-week washout period, the E group changed to L and vice versa as a cross-over design. They were followed for another 8 weeks. Before and after treatment, we checked 8-OHdG and malondialdehyde (MDA) as biomarkers of DNA damage and lipid peroxidation, respectively.8-OHdG levels were significantly decreased after treatment in the E+L+ and L+ groups (P0.001, P = 0.001, respectively). Only the TT genotype of AGT had the most antioxidative role regarding the treatment (P = 0.01). We found a remarkable correlation between MDA and DNA damage levels before and after intervention (r = 0.48, P0.001; r = 0.35, P = 0.006).The protective effects of L+ and E+L+ on DNA breaks are surprising regarding the RAS polymorphisms.

Objectives: In this study, the effect of enalapril (E) and/or losartan (L) on lipid peroxidation (LPO) is studied in renal transplant recipients (RTRs) with regard to polymorphisms of renin–angiotensin system (RAS). Design and methods: After determination of genotypes of the angiotensin-converting enzyme (ACE I/D), angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (ATR1 A1166C) by PCR, sixty-four RTRs recruited to four groups randomly: first (13 patients) and second (20 patients) groups were treated with enalapril (E + : 10 mg/day) and losartan (L + : 50 mg/day) alone for 2 months, respectively. After 2 weeks as washout period, E group changed to L and vice versa as a cross-over design and they were treated for another 2 months. The third group (13 patients) as positive control received enalapril + losartan (E + L + : 10 mg/day + 50 mg/day) for 16 weeks, and the forth group (18 patients) as negative control received no medication (E − L − ). Malondialdehyde (MDA) as LPO marker was measured before and after treatment. In this study, P Results: After 2 months of treatment, MDA level significantly decreased in all of the groups except the E − L − . MDA level in pre- vs. post-intervention for the E + L + , E + , L + and E − L − groups were as follows: 5.81 ± 2.13 nmol/mL vs. 1.61 ± 0.80 nmol/mL ( P = 0.001), 5.10 ± 2.05 nmol/mL vs. 1.68 ± 1.01 nmol/mL ( P = 0.003), 5.20 ± 1.61 nmol/mL vs. 1.22 ± 0.27 nmol/mL ( P = 0.000) and 5.27 ± 2.12 nmol/mL vs. 5.07 ± 2.03 nmol/mL ( P = 0.52), respectively. Also, the same results were found in the end of 16th week. Although patients with DD genotype of ACE had higher MDA ( P = 0.01) levels, RAS polymorphisms could not predict the antioxidative response rate to the drugs ( P > 0.05). Conclusions: E and/or L reduce MDA regardless of the RAS genotypes.

Gingival overgrowth is a complication of cyclosporine therapy following organ transplantation. Oral azithromycin is frequently used to treat this complication. This study examined the efficacy of local azithromycin, in the form of toothpaste, against cyclosporine-induced gingival overgrowth.Twenty stable renal transplanted patients (10 men and 10 women) with gingival hyperplasia were randomly assigned to a test group and a control group. Azithromycincontaining toothpaste had 85 mg azithromycin per gram of toothpaste. Both toothpastes were prescribed b.i.d., each time using 1.5 cm, for 1 month. All participants received scaling, root planing, polishing, and oral hygiene instructions, at least 4 weeks prior to initiation of the study. Gingival overgrowth index, bleeding on probing, blood urea nitrogen, creatinine, and serum cyclosporine levels were measured at baseline, and then again in the second and fourth weeks after tooth brushing. Patient satisfaction with the toothpastes was evaluated by a visual analogue scale. The stability of clinical responses was followed for 3 months after cessation of the toothpastes.Gingival overgrowth index decreased significantly in the azithromycin-containing toothpaste group (from 1.1+/-0.56 to 0.51+/-0.47, P.001); however, in the control group, this decrease was not significant (P=.22). Bleeding on probing also decreased significantly in patients in the azithromycin-containing toothpaste group compared with controls (P=.001). When compared with baseline levels, trough levels of cyclosporine, blood urea nitrogen, and creatinine did not change in either of the groups. Patients in the control group were more satisfied with the toothpaste than were patients in the test group (53 vs 38).Azithromycin-containing toothpaste is an effective, simple, and noninvasive treatment for cyclosporine-induced gingival overgrowth.

Background Hemodialysis patient are at high risk for hepatitis B virus (HBV) infection. Although preventive vaccination is done routinely, the response to vaccination is low in this patient population. The aim of this study was to evaluate the effect of Levamizol, an enhancer of the immune responsiveness, on different routs of vaccination, i.e., intradermal (ID) versus intramuscular (IM), in stable chronic hemodialysis patients. Materials and methods Forty four chronic heamodialyses patient were divided into four equal groups. The first group was received 40 μg HB vaccine intramuscularly. The second group was received 20 μg HB vaccine intradermally. The third and the fourth group received 20 μg vaccine IM or ID, respectively, in three doses plus oral Levamisole (100 mg for 12 day). After one and six months from the last dose of vaccine, HBs antibody titers were measured. Results The response rate to vaccine (HBs Antibody>10 μg/L) in the routine IM HB vaccination was low (60%). It increased to 70% with ID route. Levamisole significantly raised the response rate to 90% (P < 0.01). Also in the Levamisole groups protective HB antibody titers were maintained until the end of six months. We conclude that HD patients must be vaccinated by ID route and addition of Levamisole. Levamisole also increases antibody maintenance.

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

This study was designed to determine the effect of nandrolone decanonate (ND) on HDL-C, apolipoproteins and paraoxonase (PON) activity in stable hemodialysis patients.64 hemodialysis patients were treated with ND at a dose of 100 mg/I.M./week for 4 months. HDL-C, Apo-AI, Apo B, concentrations and PON activity were measured before and after 2 and 4 months of treatment as well as 2 months after withdrawing the treatment.After 4 months of treatment, an elevation in the serum levels of Apo B (P0.0001) and a marked decrease in the concentration of HDL-C (P0.0001), Apo-AI (P0.0001) and PON activity (P0.0001) were found. A significant correlation between PON and both Apo-AI (r=0.270, P0.04) and HDL-C (r=0.455, P0.0001) and also between HDL-C and Apo-AI (r=0.305, P0.02) were found.Results revealed the adverse effects of ND on apolipoprotein levels in our study population. It is possible that ND reduces PON activity mostly by reducing both the HDL-C and Apo-AI levels.

Malnutrition, anemia and increased atherosclerosis are the main causes of mortality in hemodialysis patients. Therapies designed to improve the disorders might therefore be expected to improve outcome. The effects of Nandrolone Decanoate (ND), in 64 stable hemodialysis patients, were studied with respect to the following parameters: nutritional status, hematological indexes, lipid profiles including serum levels of lipoprotein(a) [Lp(a)] in terms of differences in apolipoprotein(a) [apo(a)]. The patients were treated with ND at dose of 100 mg/I.M./week for 4 months. After 2 and 4 months of treatment the elevations in the serum levels of albumin (p < 0.0001), creatinine (p < 0.009), hemoglobin (p < 0.03), hematocrit (p < 0.03), cholesterol (p = 0.007) and triglyceride (p < 0.04) were noticed. Marked decrease in the concentration of high-density lipoprotein cholesterol (p = 0.007) and Lp(a) (p < 0.0001) were also found. These effects after 2 months of treatment withdrawal were relatively constant. By dividing patients according to the baseline Lp(a) levels and molecular weight of apo(a) isoform, it was noticed that the decrease in serum Lp(a) was significant in patients with high Lp(a) (>30 mg/dl) than those of with low Lp(a) (