Identification of disease specific pathways using in vivo SILAC proteomics in dystrophin deficient mdx mouse.

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by a mutation in the dystrophin gene. DMD is characterized by progressive weakness of skeletal, cardiac, and respiratory muscles. The molecular mechanisms underlying dystrophy-associated muscle weakness and damage are not well understood. Quantitative proteomics techniques could help to identify disease-specific pathways. Recent advances in the in vivo labeling strategies such as stable isotope labeling in mouse (SILAC mouse) with (13)C6-lysine or stable isotope labeling in mammals (SILAM) with (15)N have enabled accurate quantitative analysis of the proteomes of whole organs and tissues as a function of disease. Here we describe the use of the SILAC mouse strategy to define the underlying pathological mechanisms in dystrophin-deficient skeletal muscle. Differential SILAC proteome profiling was performed on the gastrocnemius muscles of 3-week-old (early stage) dystrophin-deficient mdx mice and wild-type (normal) mice. The generated data were further confirmed in an independent set of mdx and normal mice using a SILAC spike-in strategy. A total of 789 proteins were quantified; of these, 73 were found to be significantly altered between mdx and normal mice (p < 0.05). Bioinformatics analyses using Ingenuity Pathway software established that the integrin-linked kinase pathway, actin cytoskeleton signaling, mitochondrial energy metabolism, and calcium homeostasis are the pathways initially affected in dystrophin-deficient muscle at early stages of pathogenesis. The key proteins involved in these pathways were validated by means of immunoblotting and immunohistochemistry in independent sets of mdx mice and in human DMD muscle biopsies. The specific involvement of these molecular networks early in dystrophic pathology makes them potential therapeutic targets. In sum, our findings indicate that SILAC mouse strategy has uncovered previously unidentified pathological pathways in mouse models of human skeletal muscle disease.

Activation of the ubiquitin proteasome pathway in a mouse model of inflammatory myopathy: a potential therapeutic target.

OBJECTIVE: Myositis is characterized by severe muscle weakness. We and others have previously shown that endoplasmic reticulum (ER) stress plays a role in the pathogenesis of myositis. The present study was undertaken to identify perturbed pathways and assess their contribution to muscle disease in a mouse myositis model. METHODS: Stable isotope labeling with amino acids in cell culture (SILAC) was used to identify alterations in the skeletal muscle proteome of myositic mice in vivo. Differentially altered protein levels identified in the initial comparisons were validated using a liquid chromatography tandem mass spectrometry spike-in strategy and further confirmed by immunoblotting. In addition, we evaluated the effect of a proteasome inhibitor, bortezomib, on the disease phenotype, using well-standardized functional, histologic, and biochemical assessments. RESULTS: With the SILAC technique we identified significant alterations in levels of proteins belonging to the ER stress response, ubiquitin proteasome pathway (UPP), oxidative phosphorylation, glycolysis, cytoskeleton, and muscle contractile apparatus categories. We validated the myositis-related changes in the UPP and demonstrated a significant increase in the ubiquitination of muscle proteins as well as a specific increase in ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL-1) in myositis, but not in muscle affected by other dystrophies or normal muscle. Inhibition of the UPP with bortezomib significantly improved muscle function and also significantly reduced tumor necrosis factor α expression in the skeletal muscle of mice with myositis. CONCLUSION: Our findings indicate that ER stress activates downstream UPPs and contributes to muscle degeneration and that UCHL-1 is a potential biomarker for disease progression. UPP inhibition offers a potential therapeutic strategy for myositis.

Determination of oxidative stress and cellular inflammation in patients with diabetic nephropathy and non-diabetic nephropathy being administered hemodialysis treatment due to chronic renal failure.

OBJECTIVES: We aimed to evaluate oxidative stress [8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA)] endothelial damage [asymmetric dimethylarginine (ADMA)] and markers of cellular inflammation [interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), neopterin (NP) and high-sensitivity C-reactive protein (hsCRP)] in patients with diabetic nephropathy (DN) and non-diabetic nephropathy who were being administered hemodialysis treatment because of chronic renal failure. METHODS: In determining 8-OHdG, IL-6 and TNF-α levels, Enzyme-Linked Immuno-Sorbent Assay method was used. Serum MDA, ADMA and NP levels were determined by using high performance liquid chromatography (HPLC). And hs-CRP values were measured with nephelometric method. RESULTS: Serum 8-OHdG and MDA levels were found statistically to have increased when compared with those of the control group in patients groups after dialysis. However, serum ADMA and neopterin levels were observed statistically to have decreased when compared with those of the control group in patients groups after dialysis. But, decreases on ADMA and neopterin levels are still much higher than those of control. IL-6 and TNF-α levels were found to have increased when compared with those of control group in patients groups before dialysis. CONCLUSION: The oxidative stress in patients with DN, who were being treated with hemodialysis due to chronic renal failure, was higher than that of non-DN patients who were being treated with hemodialysis. In contrast with this, inflammation occurring in non-DN patients was found to have been higher than that of in patients with DN.

Neutrophil to lymphocyte ratio independently predicts cardiovascular events in patients with chronic kidney disease.

BACKGROUND: Increased inflammation is common in patients with chronic kidney disease (CKD) and is associated with increased adverse cardiovascular events (CVE). Neutrophil-to-lymphocyte ratio (NLR) was used to predict survival in patients with acute coronary syndrome. We aimed to evaluate predictive ability of NLR in CKD patients. METHODS: 225 subjects with stage 3-5 CKD were followed for a mean of 39 months. Fatal and nonfatal CVE were recorded during this period. NLR at baseline was determined from complete blood count differential. Endothelial dysfunction (flow-mediated dilation, FMD), hsCRP and insulin resistance were determined. We investigated if NLR could predict development of fatal and nonfatal CVE. We also looked at how NLR and its individual components change across CKD stages and whether NLR is related to CRP, insulin resistance and endothelial dysfunction. RESULTS: There were 70, 74 and 81 patients in groups of CKD stage-3, stage-4 and stage-5, respectively. Median NLR was 2.81. NLR showed a significant increase from stage 3 to stage 5. NLR was inversely associated with FMD independent of hsCRP. 14 fatal and 52 nonfatal CVE occurred during follow-up period. NLR could predict composite CVE independent of insulin resistance and hsCRP. Increased NLR over 2.81 was related to a significantly decreased survival time (log-rank Chi-square = 14.833, P < 0.0001). A cutoff value for NLR ≥3.76 could predict development of composite CVE with 80.3 % sensitivity and 91.8 % specificity. CONCLUSIONS: NLR is independently related to endothelial dysfunction and could predict composite cardiovascular endpoints independent of traditional confounding factors in patients with moderate to severe CKD.

Serum uric acid independently predicts cardiovascular events in advanced nephropathy.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk for cardiovascular (CV) disease and is also associated with elevated uric acid, which is emerging as a nontraditional CV risk factor. We therefore evaluated uric acid as a risk factor for CV disease in subjects presenting to nephrologists with CKD who were not on medications known to alter endothelial function. METHODS: 303 subjects with stage 3-5 CKD were followed for a mean of 39 months (range 6-46) and assessed for fatal and nonfatal CV events. Hyperuricemia was defined as uric acid >6.0 mg/dl for women and >7.0 mg/dl for men. In addition to other CV risk factors, endothelial function (flow-mediated dilatation), inflammatory markers (hsCRP), and insulin resistance (HOMA index and fasting insulin levels) were included in the analysis. We evaluated the association between uric acid and flow-mediated dilatation with linear regression. The impact of uric acid on composite CV events was assessed with Cox regression analysis. RESULTS: Of a total of 303 patients, 89 had normouricemia and 214 had hyperuricemia. Both fatal (32 of 214 vs. 1 of 89 subjects) and combined fatal and nonfatal (100 of 214 vs. 13 of 89 subjects) CV events were more common in subjects with hyperuricemia compared with normal uric acid levels, and this was independent of estimated glomerular filtration rate, traditional CV risk factors including diabetes, hypertension and BMI, and nontraditional risk factors (hsCRP and endothelial function). The 46-month survival rate was 98.7% in the group with low uric acid compared to 85.8% in patients with high uric acid (p = 0.002). CONCLUSIONS: Hyperuricemia is an independent risk factor for CV events in subjects presenting with CKD who are not on medications known to alter endothelial function.

Protective effects of melatonin and S-methylisothiourea on mechlorethamine induced nephrotoxicity.

BACKGROUND: In this study, we aimed to investigate the protective effects of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced nephrotoxicity. MATERIALS AND METHODS: A total of 36 male Sprague-Dawley rats were divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Three groups received single dose of MEC (3.5 mg/kg) via transdermal route. Control animals were given saline only via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC. RESULTS: The tissue TNF-α, IL-1ß, and NOx levels were found significantly different for all groups (P < 0.001). MEC application resulted in severe histopathological changes. Melatonin showed meaningful protection against kidney damage. But protection by SMT was weaker. TNF-α and IL-1ß levels increased significantly with MEC application, and MEL and SMT ameliorated these increases in kidney tissue. MEC also elevated NOx levels in kidney tissue. CONCLUSIONS: Both inflammation and oxidative stress may have an important role in the MEC induced nephrotoxicity. MEL and SMT may also have anti-inflammatory properties, as well as anti-oxidant properties.

Serum lactate dehydrogenase levels significantly correlate with radiological extent of disease and spirometric values in patients with silicosis due to denim sandblasting.

BACKGROUND: The aim of the present study was to investigate serum lactate dehydrogenase (LD) levels in patients with silicosis due to denim sandblasting (SDDS) and also to investigate possible correlations between serum LD levels and the degree of radiological extent of disease (RED) and pulmonary function tests. METHODS: Forty-four males with SDDS and 32 healthy male subjects were included in the study. Patients and healthy controls were compared for serum LD levels. Correlations between serum LD levels, RED and spirometric values were investigated. RESULTS: Patients with SDDS had significantly higher serum LD levels than healthy controls. Patients with complicated SDDS had significantly higher serum LD levels than patients with simple SDDS. Significant correlations were found between serum LD levels and RED values. Significant correlations were found between serum LD levels and spirometric parameters. CONCLUSIONS: High serum LD levels might be considered as a marker of pulmonary parenchymal involvement in patients with SDDS. This study also suggests that the increase in serum LD levels might be closely related to the degree of pulmonary involvement in SDDS patients.

Asymmetrical dimethylarginine levels on the implantation success of in vitro fertilization and embryo transfer.

The aim of this study was to evaluate the level of asymmetrical dimethylarginine (ADMA) levels before gonadotrophine treatment and on the day of oocytes retrieval in order to determine whether ADMA can be used as a predictive marker for implantation success in in vitro fertilization (IVF) cycles. Forty-four unexplained infertile patients were included in the study. Controlled ovarian hyperstimulation was performed using the recombinant follicle-stimulating hormone (FSH) with the standard long protocol for all patients. ADMA and E2 were measured at the beginning of the ovulation induction and on oocyte retrieval day. The primary outcome was the difference in ADMA levels in implantation positive and implantation negative women. At the beginning of the ovulation induction, the mean ADMA levels were 1553 µmol/L and 1.464 µmol/L in the implantation positive and negative groups, respectively. There was no statistically significant difference between groups (p: 0.90). On the day of oocyte retrieval, the mean ADMA levels were 1173 µmol/L and 1170 µmol/L in the implantation positive and negative groups, respectively. There was no statistically significant difference between groups (p: 0.97). In conclusion, ADMA levels before gonadotrophine treatment and the day of oocytes retrieval cannot be used as a predictive marker for implantation success in IVF cycles.

Paraoxonase lactonase activity (PON-HTLase), asymmetric dimethylarginine (ADMA) and platelet activating factor-acetylhydrolase (PAF-AH) activity in non-obese women with PCOS.

OBJECTIVE: Paraoxonase1 (PON1), exhibits both esterase activity (PON1-AREase) and homocysteine thiolactonase activity (PON1-HTLase) which respectively prevent LDL oxidation and detoxify homocysteine thiolactone (HTL). Platelet-activating factor-acetylhydrolase (PAF-AH) is an antioxidant enzyme preventing LDL oxidation by hydrolysis of oxidized phospholipids. Both of these enzymes exhibit a proatherogenic role. ADMA is an endogenous inhibitor of nitric oxide (NO) synthesis causing endothelial dysfunction. The aim was to compare non-obese PCOS patients with a BMI matched control group using the following characteristics: serum PON1-HTLase, ADMA, PAF-AH, and lipid and hormonal parameters. RESULTS: 77 women with PCOS and 25 healthy subject were recruited for this study, The controls were non-obese BMI and age matched with the patients. There were no significant differences with respect to age, BMI, FSH, free testosterone, DHEA, androstenadion, total cholesterol, triglycerides, HDL, LDL, VLDL, fasting glucose/insulin ratio and HOMA-IR among the groups (p > 0.05). However, total testosterone and fasting glucose levels were significantly higher in the PCOS group (p < 0.05). On the other hand, PON1-HTLase levels (39.6 ± 5.77 vs. 33.8 ± 8.2, p = 0.02) were significantly lower in the PCOS group while ADMA levels (1.14 ± 0.6 vs. 3.37 ± 6.4, p = 0.004) were significantly higher in the PCOS group. However, there was no significant difference in PAF-AH activity among the groups. CONCLUSIONS: Decreased PON1-HTLase and increased ADMA levels might be a relevant marker for the development of future atherosclerotic heart disease (AHD) in non-obese PCOS patients. Further studies are needed to confirm our results.

The effects of medical ozone therapy on renal ischemia/reperfusion injury.

INTRODUCTION: This study was designed to investigate the possible beneficial effects of medical ozone therapy (OT), known as an immunomodulator and antioxidant, on the renal function, morphology, and biochemical parameters of oxidative stress in kidneys subjected to ischemia/reperfusion injury (IRI). MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were classified into three groups: control, renal IRI, and renal IRI + OT. The IRI group was induced by bilateral renal ischemia for 60 min, followed by reperfusion for 6 h. After reperfusion, the kidneys and blood of rats were obtained for histopathologic and biochemical evaluation. RESULTS: Renal IRI increased the tissue oxidative stress parameters (lipid peroxidation, protein oxidation, and nitrite plus nitrate) and decreased the antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase). The serum neopterin levels showed correlation with oxidative stress parameters. All these parameters were brought to control values in the treatment group. Histopathologically, the kidney injury in the treatment group was significantly lesser than in the renal IRI group. CONCLUSIONS: Our results clearly showed that OT has beneficial effect to protect kidney against IRI. The serum neopterin levels might be used as a marker to detect the degree of renal IRI.

Simultaneous determination of cyclosporine A, tacrolimus, sirolimus, and everolimus in whole-blood samples by LC-MS/MS.

OBJECTIVES: Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and everolimus (RAD) are immunosuppressive drugs frequently used in organ transplantation. Our aim was to confirm a robust sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of CyA, TRL, SIR, and RAD in whole-blood samples. MATERIALS AND METHODS: We used an integrated online solid-phase extraction-LC-MS/MS system and atmospheric pressure ionization tandem mass spectrometry (API-MS/MS) in the multiple reaction monitoring (MRM) detection mode. CyA, TRL, SIR, and RAD were simultaneously analyzed in whole blood treated with precipitation reagent taken from transplant patients. RESULTS: System performance parameters were suitable for using this method as a high-throughput technique in clinical practice. The high concentration of one analyte in the sample did not affect the concentration of other analytes. Total analytical time was 2.5 min, and retention times of all analytes were shorter than 2 minutes. CONCLUSION: This LC-MS/MS method can be preferable for therapeutic drug monitoring of these immunosuppressive drugs (CyA, TRL, SRL, and RAD) in whole blood. Sample preparation was too short and simple in this method, and it permits robust, rapid, sensitive, selective, and simultaneous determination of these drugs.

Serum uric acid level and endothelial dysfunction in patients with nondiabetic chronic kidney disease.

BACKGROUND: An elevated serum uric acid level is strongly associated with endothelial dysfunction and inflammation, both of which are common in chronic kidney disease (CKD). We hypothesized that endothelial dysfunction in subjects with CKD would correlate with uric acid levels. MATERIALS AND METHODS: We evaluated the association between serum uric acid level and ultrasonographic flow-mediated dilatation (FMD) in 263 of 486 patients with recently diagnosed CKD (stage 3-5) (48% male, age 52 ± 12 years). To minimize confounding, 233 patients were excluded because they were diabetic, had established cardiovascular complications or were taking drugs (renin-angiotensin system blockers, statins) interfering with vascular function. RESULTS: Serum uric acid level was significantly increased in all stages of CKD and strongly correlated with estimated glomerular filtration rate (eGFR-MDRD); FMD was inversely associated with serum uric acid (r = -0.49, p < 0.001). The association of serum uric acid with FMD remained after adjustment for age, gender, smoking, LDL cholesterol, eGFR, high-sensitivity C-reactive protein, systolic blood pressure, proteinuria, and homeostatic model assessment index (ß = -0.27, p < 0.001). CONCLUSION: Increased serum uric acid is an independent predictor of endothelial dysfunction in subjects with CKD.

Serum prolidase activity in patients with pulmonary tuberculosis.

AIM: To investigate serum prolidase activity (SPA) in patients with pulmonary tuberculosis (PTB). MATERIAL AND METHODS: Twenty-nine PTB patients and 32 controls were included in the study. PTB patients (cavitary and non-cavitary) and controls were compared in terms of mean SPA. Correlations were evaluated between SPA and acute phase reactants. RESULTS: Mean SPA was significantly higher in PTB patients than in the control group. Mean SPA was significantly higher in patients with cavitary TB than non-cavitary TB. Mean SPA in patients with mild PTB was lower than patients with moderate and severe disease. We found significant correlations between SPA and CRP, ESR, albumin, platelet counts, HDL-cholesterol and LDH activity. CONCLUSION: This study has shown that PTB patients have higher SPA than controls. The increase in SPA might be related to tissue destruction, increased immunoglobulin, complement levels and increased fibroblastic activity; all of which are involved in the natural history of PTB.

Comparison of hyperbaric oxygen and medical ozone therapies in a rat model of experimental distal colitis.

OBJECTIVES: Previous studies have shown that hyperbaric oxygen (HBO) is effective in reducing the severity of acute distal colitis (ADC). Ozone therapy (OT) reduces inflammation in several pathological conditions. We aimed to compare the effects of HBO therapy and OT in an experimental ADC rat model. MATERIALS AND METHODS: Forty rats were randomly divided into four groups: Sham, ADC, ADC + HBO, and ADC + OT. Rats in the sham group were given isotonic saline. In the remaining groups, ADC was created by intracolonic administration of 4% acetic acid. No treatment was given to the ADC group. The rats in the ADC + HBO and ADC + OT groups were given HBO and ozone treatments, respectively. The administration of acetic acid caused an inflammatory response in all animals. Distal colons and blood samples were obtained. RESULTS: The histopathological score was significantly higher in the ADC group compared to the other groups. The histopathological scores in the ADC + HBO and ADC + OT groups were significantly lower compared to the ADC group (both p < 0.001). The most pronounced therapeutic effect was observed in the ADC + OT group. Malondialdehyde and neopterin levels and superoxide dismutase and glutathione peroxidase activities in the ADC group were significantly higher compared to the other groups (p < 0.001). CONCLUSION: Our data showed that the therapeutic effect of OT is more pronounced than that of HBO therapy. Its possible effect is by means of decreasing inflammation, edema, and oxidative stress. These findings also suggest that it is possible to improve the outcome of ADC by using ozone therapy as an adjuvant therapy.

The levels of nitric oxide and asymmetric dimethylarginine in the rat endometriosis model.

AIM: To investigate the levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA) in all the rat endometriosis models. MATERIAL & METHODS: Forty-one rats with endometriotic implants were divided into four groups (1 to 4) and administered infliximab, etanercept, letrozole and control, respectively. There were 11 rats in group 5 (normal). The size of implants, plasma ADMA and nitrate/nitrite (NO(x) ) levels and histological score were assessed. RESULTS: In groups 1, 2 and 3, plasma ADMA levels were higher than groups 4 and 5, 296.8 ± 66.2, 285.9 ± 35.7, 200.3 ± 41.0, 125.3 ± 16.7, 111.3 ± 6.5 µmol/L, respectively, while NO(x) levels were lower than groups of control and normal 19.6 ± 3.8, 19.8 ± 4.4, 39.3 ± 6.1, 80.5 ± 5.3, and 91.1 ± 5.0 µmol/L, respectively. CONCLUSIONS: Infliximab, etanercept and letrozole have regressed endometriotic implants, decreased plasma NO(x) levels, and increased plasma ADMA levels.

Beneficial effects of N-acetylcysteine and ebselen on renal ischemia/reperfusion injury.

INTRODUCTION: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations. RESULTS: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups. CONCLUSIONS: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.

Effect of nail polish and henna on oxygen saturation determined by pulse oximetry in healthy young adult females.

OBJECTIVE: The purpose of this study was to determine the effect of different colour nail polishes and henna on the measurement of oxygen saturation and the differences among the measurements of three pulse oximetry devices. MATERIAL AND METHODS: 33 healthy females with a mean age of 19±1.0 years and no complaints or known disease were included into the study. All the participants applied henna to one of their fingers a day before the study. Just before the study, one finger was left empty as control and the other fingers were dyed using various colours of nail polish (red, blue, beige, purple, brown, white, pink, green, colourless polish, light blue, light green and yellow). There were more than eight colour nail polishes and some fingers were used for the other colours after being completely cleaned. The same brand nail polishes were used for the study. Oxygen saturation measurements were done using three different pulse oximetry devices (device I, II, III) from the control, different colour nail polished and henna applied fingers. The measurements of different devices, different colour nail polishes, henna and control were statistically compared. RESULTS: The mean saturations obtained from blue, beige, purple and white nail polished fingers were significantly lower than those of control and the other coloured fingers. In addition, the mean measurement of device II was significantly lower than those of other devices. CONCLUSION: The results suggest that blue, beige, purple and white nail polished fingers might cause pulse oximetry devices to make incorrect measurements.

The role of asymmetric dimethyl arginine and oxidant/antioxidant system in preeclampsia.

Preeclampsia is a syndrome characterized by hypertension and proteinuria. The aim of this study is to find the relationship between preeclampsia, asymmetric dimethyl arginine (ADMA), and the oxidant/antioxidant system. Twenty-one preeclamptic and 28 normal pregnant women were included in this study. In cord bloods, ADMA and oxidant/antioxidant parameters were measured. Asymmetric dimethyl arginine levels were significantly increased in preeclamptic pregnancies compared to the control group (p = 0.006). The activities of antioxidant enzymes and malondialdehyde levels were increased in the preeclamptic group compared to the control group (p < 0.001, p = 0.022, p < 0.001, p < 0.001, respectively). Development of endothelial dysfunction and oxidative stress may play a role in developing preeclampsia.

Cord blood and maternal serum neopterin concentrations in patients with pre-eclampsia.

BACKGROUND: Pre-eclampsia is a syndrome characterized by hypertension and proteinuria. The aim of this study was to investigate neopterin concentrations in cord blood and maternal serum in patients with pre-eclampsia and a control group. METHODS: Cord blood and maternal serum neopterin were measured in 21 patients with pre-eclampsia and in 27 control subjects. Neopterin concentrations were measured by high performance liquid chromatography. RESULTS: Cord blood neopterin concentrations were significantly increased in patients with pre-eclampsia compared to controls (54.3+/-16.8 vs. 43.4+/-8.5 nmol/L, p=0.011, respectively). Maternal serum neopterin (257.3+/-36.8 vs. 150.9+/-33.8 nmol/L, p<0.001) was also higher in patients with pre-eclampsia. CONCLUSIONS: Cord blood and maternal serum neopterin concentrations are higher in patients with pre-eclampsia. Maternal serum neopterin concentrations used may be used as a marker for the early diagnosis of pre-eclampsia.

Effect of renin-angiotensin-aldosterone system (RAAS) blockade on visfatin levels in diabetic nephropathy.

AIM: Plasma visfatin levels are elevated in diabetic nephropathy in parallel to the severity of proteinuria and glomerular filtration rate. The aim of this study was to find out whether the renin-angiotensin-aldosterone system (RAAS) blockage has any effect on the plasma visfatin levels. METHODS: Thirty-two patients with diabetic proteinuria (>500 mg/day) with a normal glomerular filtration rate (GFR) and 33 healthy subjects were enrolled. Patients were treated with ramipril 5 mg daily for 2 months. Proteinuria, GFR, high-sensitivity C-reactive protein (hsCRP), visfatin, flow-mediated dilatation (FMD) and homeostasis model assessment of insulin resistance (HOMA-IR) index measurements were performed both before and after the treatment. RESULTS: The plasma visfatin, and hsCRP levels of the patients were significantly higher and the FMD was significantly lower (P < 0.001 for all). The visfatin levels were significantly correlated to FMD, systolic and diastolic blood pressures, proteinuria, eGFR, HOMA-IR and hsCRP. Ramipril treatment resulted in a significant decrease in plasma visfatin, proteinuria, hsCRP, HOMA-IR and increase in FMD (P < 0.001) in patients (P < 0.001 for all). CONCLUSION: The present study suggests that plasma visfatin levels are related to the endothelial functions, inflammation and the severity of proteinuria in diabetic nephropathy. Treatment with ramipril causes a significant decrease in visfatin levels along with the improvement of proteinuria, endothelial dysfunction and inflammatory state in diabetic nephropathy.