Linkage of Fibroblast Growth Factor 23 and Phosphate in Serum: Phosphate and Fibroblast Growth Factor 23 Reduction by Increasing Dose of Sevelamer

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 < 0.05) compared with the CKD control rats. A dose-dependent decrease in serum FGF-23 levels was observed, and the most significant results were obtained in rats receiving 3% sevelamer compared with the CKD control rats (142.60±83.95 pg/mL vs. 297.15±131.10 pg/mL, P < 0.01). CONCLUSIONS: Higher sevelamer doses significantly reduced serum phosphate and FGF-23 levels in adenine-induced CKD rats.

[Polymorphisms of vitamin D receptor gene [Apa I and Fok I] and its association with serum vitamin D and parathyroid hormone levels in hemodialysis patients]

Background and Objectives: Vitamin-D recptor [VDR], plays a key role in the development of cardiovascular diseases in hemodialysis patients via the modulation of the serum levels of calcium and parathyroid hormone. In this study, we aimed to determine the genetic association of VDR gene polymorphisms with serum levels of vitamin D, parathyroid hormone and fetuin-A in hemodialysis patients

Material and Methods: Forty six hemodialysis patients and 43 control cases were studied. VDR Genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism. The serum levels of iPTH, Fetuin-A and Vit D were measured by enzyme-linked immunosorbent assay

Results: There was no significant difference in the genotype frequencies between two study groups in both Fok I and Apa I polymorphisms [p=0.2]. There was significant difference in serum iPTH levels in Fok I polymorphism [p=0.02] and Vit D levels in Apa I polymorphism [p=0.04]. Although a significant positive correlation between iPTH and Vitamin D levels in aa genotype of patients [p=0.02, r=0.4] and Vit D and Fetuin-A levels in FF genotype of control group [p=0.001, r=1] was seen

Conclusion: Polymorphisms of VDR gene Fok I and Apa I play a key role in the development of cardiovascular diseases in hemodialysis patients

Osteoprotegerin and soluble receptor activator of nuclear factor-kappa B ligand in exudative age-related macular degeneration

Calcification and inflammation are among the important cases of exudative age-related macular degeneration [E-ARMD]. The aim of the present study was to elucidate if there is any relationship between serum Osteoprotegerin [OPG], soluble receptor activator of nuclear factor-kappa B ligand [RANK-ligand] and E-ARMD. In a cross-sectional study, we compared 45 E-ARMD patients with 45 matched controls. Diagnosis was confirmed by fluorescein angiography. Serum samples were analyzed for OPG, RANK-ligand, low density lipoprotein cholesterol [LDL-C], high density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglyceride [TG]. The levels of OPG and RANK-ligand were measured by ELISA methods. The mean age was 72.0 +/- 11.5 years in the E-ARMD group and 68.2 +/- 8.9 years in the control group [p=0.09]. The level of serum OPG was 132.10 +/- 75.49 pg/ml in the E-ARMD group and 94.88 +/- 61.65 pg/ml in the control subjects. E-ARMD patients had significantly high levels of OPG [p=0.012], as well as significantly high levels of LDL-C and TC [p=0.001 and p=0.005, respectively]. We could not find any significant difference in RANK-ligand, HDL-C, or TG between two study groups [p>0.05]. To the best of our knowledge, this is the first study investigating the levels of OPG in E-ARMD patients. The present study showed that E-ARMD patients had high levels of serum OPG. It may act as a protective factor for E-ARMD or only as a secondary phenomenon of different processes of E-ARMD. Further prospective studies would be necessary for prognostic and predictive significance of OPG in patients affected by E-ARMD

High-sensitivity C-reactive protein and tumor necrosis factor alpha in pseudoexfoliation syndrome

The purpose of the present study was to determine the alterations in high-sensitivity C-reactive protein and Tumor Necrosis factor alpha levels in the blood serum of pseudoexfoliation syndrome cases [a disease with similar risk factors as systemic endothelial dysfunction diseases] and to compare the results with healthy individuals. High-sensitivity C-reactive protein and Tumor Necrosis factor alpha levels were determined in 30 cases with pseudoexfoliation syndrome and in 30 control patients of the same age and sex, by enzyme-linked immunosorbent assay. The levels of high- sensitivity C-reactive protein and Tumor Necrosis factor alpha in the blood serum of patients with pseudoexfoliation syndrome [3.95 +/- 0.88 mg/1, 332 +/- 0.99 pg/ml, respectively] were significantly higher than in the control group [2.51 +/- 0.79mg/l 0.43 +/- 0.15 pg/ml, respectively] p=0.001, p=0.002. The results suggest that increased levels of high-sensitivity C-reactive protein and Tumor Necrosis factor alpha, as markers of inflammation and peripheral endothelial dysfunction in pseudoexfoliation syndrome, may be risk factors for systemic and ocular manifestations of pseudoexfoliation syndrome

Influence of chemotherapy on the lipid peroxidation and antioxidant status in patients with acute myeloid leukemia

Chemotherapeutic agents used in patients with cancer cause to generate the enormous amounts of free radicals associated with cell injury. In this study we assess the effects of chemotherapy regimen on oxidant/antioxidant status in patients with acute myeloid leukemia [AML]. 38 newly diagnosed patients with acute myeloid leukemia were recruited in this study. All patients received cytarabine and daunorubicin as chemotherapy regimen. Plasma levels of malondialdehyde [MDA], total antioxidant status [TAS], and the levels of erythrocyte activity of superoxide dismutase [SOD] and glutathione peroxidase [GPx] were determined before chemotherapy and 14 days after chemotherapy with cytarabine and daunorubicin. Plasma MDA concentrations increased significantly [from 2.68 +/- 0.89 nmol/L to 3.14 +/- 1.29 nmol/L] during the 14days post-chemotherapy period [P=0.04]. Plasma TAS concentrations changed with chemotherapy from 1.09 +/- 0.15 mmol/L to 1.02 +/- 0.14 mmol/L with P=0.005. Erythrocyte SOD and GPX activity decreased overtime from 1157.24 +/- 543.61 U/g Hb to 984.01 +/- 419.09 U/g Hb [P=0.04] and 46.96 +/- 13.70 U/g Hb to 41.40 +/- 6.44 U/g Hb [P=0.02] respectively. We report here that there is an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant status. This suggests that chemotherapy causes these changes as a result of enormous production of reactive oxygen species in the patients with AML. Antioxidant supplementation must be approached with caution because of the probability of reduction the therapeutic efficacy of these cytotoxic drugs.

Association between serum ferritin and circulating oxidized low-density lipoprotein levels in patients with coronary artery disease

Oxidation of low-density lipoprotein [LDL] is believed to be a key factor in the development of atherosclerosis. Oxidative modification of LDL is associated with increased uptake of these particles by the macrophage receptors located in the arterial wall which in turns would lead to accumulation of lipids within the cytoplasm of the cell and formation of the foam cells, a perquisite step in the development of the atherosclerotic plaque. The aim of the present study was to evaluate the association between serum Ferritin and oxidized low-density lipoprotein in coronary artery disease [CAD] patients. The study group consisted of 160 males [mean age [47 +/- 7] years] with suspected CAD and no history of renal, liver and diabetic disorders undergoing coronary angiography. Oxidized LDL and Ferritin levels were measured by ELISA methods. Results obtained from the study revealed that the mean serum Ferritin concentration in our study population was 149.77+119.93 ng/ml and that of OX-LDL was 8.86+5.67 IU/L. Serum Ferritin levels were significantly correlated with both OX-LDL concentrations [p=0.001, r=0.24] and CAD SCORE [p=0.005, r=0.208] in study patients group; however no correlation was detected between OX-LDL and CAD SCORE [p>0.9]. The present study is the first to report serum Ferritin levels is associated with circulating OX-LDL level in patients with CAD. The correlation of CAD SCORE with Ferritin levels in these patients is indicative of the importance of this parameter in predicating CAD. These results suggest that measurement of OX- LDL and Ferritin could be of great assistance in predicating premature CHD.

Effect of fish oil supplements on serum paraoxonase activity in female patients with rheumatoid arthritis: a double-blind randomized controlled trial

This study was conducted to determine the effect of fish oil [FO] supplements on high density lipoprotein cholesterol [HDL-C], apolipoprotein-Al [Apo-Al], 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-Al, and MDA levels as well as POW 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 Pearson's test and the statistical significance was set at P < 0.05. 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-Al [P = 0.165], Aryl [P = 0.026], and POW [P = 0.049] activity increased, whereas MDA levels decreased significantly with FO supplementation [P= 0.077]. Significant correlations between increased POW activity and both HDL-C [P = 0.007, r = 0.419] and Apo-Al [P < 0.001, r = 0.742] concentrations as well as between HDL-C and Apo Al levels [P= 0.01, r = 0.403] were found. According to the results of this study, EQ could increase serum HDL-C and PQN1 levels and Aryl activity in female patients with RA

C-reactive protein level following treatment and withdrawal of lovastatin in diabetic nephropathy

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

Enhanced susceptibility of low-density lipoprotein to oxidation in wet type age-related macular degeneration in male patients

To determine the susceptibility of low-density lipoprotein [LDL] to oxidation in the plasma of male patients with wet type age related macular degeneration [AMD] and in a similar control group, in order to evaluate the LDL oxidative status as risk factor of AMD. We conducted this study in the Retina Service, Department of Ophthalmology, Nikookari Eye Hospital ' Drug of Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran during the period between October 2004 and December 2005. Sixty male patients with AMD [mean age 67 +/- 16 years] with BMI 4.1 +/- 1.3 were selected as the patient group. The control group consisted of 60 males, apparently healthy, and without ophthalmologic signs and family history of AMD. Low-density lipoprotein was isolated by gradient ultracentrifugation and susceptibility of LDL to in vitro copper-mediated oxidation was assayed by measuring conjugated dienes production [lag phase duration] at 234 nm. Lipid and lipoproteins were determined by standard methods. Comparing with control, significant reduction in the duration of lag phase [p<0.004] and a significant increase in LDL-C concentrations [p=0.006], were noticed. No significant change in cholesterol [p>0.3], triglyceride [p>0.1] and high density lipoprotein cholesterol [p>0.1] levels were found between control and patient groups. A significant negative correlation between Lag phase and LDL-C levels [p=0.004, r=-0.364] was found in the patient group. The increased LDL concentration and enhanced susceptibility of LDL to oxidation may play a roll in the wet type AMD process