Cengizhan Acikel

Short-Term Treatment with Sevelamer Increases Serum Fetuin-A Concentration and Improves Endothelial Dysfunction in Chronic Kidney Disease Stage 4 Patients

BACKGROUND AND OBJECTIVES Vascular calcification and endothelial dysfunction contribute to the development of cardiovascular disease in patients with chronic kidney disease (CKD). Sevelamer, a non-calcium-based phosphate binder, has been shown to attenuate cardiovascular calcification in CKD patients, although the exact mechanism has not been clarified. This study was designed to investigate the effect of short-term sevelamer treatment on both serum fetuin-A concentrations and endothelial dysfunction seen in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Fifty nondiabetic stage 4 CKD patients whose phosphate levels were > or =5.5 mg/dl were enrolled in this 8-wk randomized prospective study. Thirty-six healthy volunteers served as matched controls. Patients were treated with either sevelamer (n = 25, 12 males) or calcium acetate (n = 25, 13 males). Fetuin-A, high-sensitivity C-reactive protein, Ca x PO4 product, flow-mediated dilation (FMD), insulin, and homeostasis model assessment (HOMA) were obtained at baseline and after the treatment period. RESULTS As expected, CKD patients had significantly lower levels of fetuin-A and FMD, and significantly higher levels of intact parathyroid hormone, Ca x PO4 product, and high-sensitivity C-reactive protein than controls (P < 0.001 for all). The use of sevelamer led to a significant increase in the fetuin-A concentration with improvement in FMD, whereas no significant difference was observed in the calcium acetate group. In a multiple regression analysis, FMD levels were independently related to fetuin-A both before (beta = 0.63, P < 0.001) and after (beta = 0.38, P = 0.004) treatment. CONCLUSIONS This small, randomized, prospective study shows that short-term sevelamer treatment significantly increases fetuin-A levels and improves FMD in nondiabetic stage 4 CKD patients.

Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome

Aim:  Plasma adiponectin levels are well associated with metabolic syndrome. However, the relationship between hypertension and plasma adiponectin levels is not clear. Also, there is not enough data about the effects of different antihypertensive regimens on plasma adiponectin levels.

Endothelial functions improve with decrease in asymmetric dimethylarginine (ADMA) levels after renal transplantation.

Background. Chronic kidney disease (CKD) is associated with increased cardiovascular events. The relationships between the markers of inflammation and endothelial dysfunction were investigated both before and after living donor kidney transplantation. Methods. Twenty-seven renal transplant patients were studied. Eleven patients (six male, five female) were on cyclosporine A, whereas 16 patients (nine male, seven female) were treated with tacrolimus based regimes. Twenty-seven subjects (12 males, 15 females) were studied as controls. Plasma adiponectin, high sensitive C reactive protein (hsCRP), Asymetric dimethyl arginine (ADMA) levels were studied before transplantation and on days 1, 3, 7, 14, and 28. The brachial artery flow mediated dilatation (FMD) was studied before transplantation and on the 28th day. Results. Serum hsCRP and ADMA levels decreased significantly from the first posttransplantation day on each measurement (P<0.001 for all) while the decrement of plasma adiponectin started in the third day (P<0.001 for all). The FMD was lower in the patients than the control group (P<0.001) and improved significantly in the 28th day of transplantation (P<0.001). Conclusions. The results indicate that ADMA is associated with FMD in CKD both before and after kidney transplantation. Endothelial functions improve at the very beginning of the posttransplantation period with accompanying reduction in ADMA and hsCRP levels.

Relationship between Serum Magnesium Levels and Cardiovascular Events in Chronic Kidney Disease Patients

Background: Magnesium is an essential ion for all living cells because over 300 enzymes require the presence of magnesium for their catalytic action. To date, no group has evaluated magnesium as a cardiovascular risk factor in chronic kidney disease (CKD) subjects, in which closely interrelated factors and potential confounders such as endothelial dysfunction, insulin resistance (the homeostasis model assessment (HOMA) index) and inflammation (expressed as serum C-reactive protein (CRP) levels) were also considered. Methods: Between March 2006 and December 2010, 283 CKD patients were followed up for time-to-event analysis until the occurrence of fatal or nonfatal cardiovascular events. Endothelium-dependent vasodilatation (flow-mediated dilatation; FMD) and endothelium-independent vasodilatation (nitroglycerin-mediated dilatation) of the brachial artery were assessed noninvasively using high-resolution ultrasound. Results: From the univariate analysis of FMD, it appears that a higher magnesium level is associated with less endothelial dysfunction. When a multivariate analysis was performed, magnesium and estimated glomerular filtration rates (eGFR) maintained a strong positive correlation with FMD, supporting the hypothesis that higher levels of magnesium may protect against endothelial damage. In univariate Cox proportional hazards models, FMD, magnesium, high sensitivity CRP, the HOMA index, eGFR, comorbid diabetes, hypertension, smoking status, systolic blood pressure, serum phosphate and intact parathormone emerged as significant predictors for cardiovascular outcomes. Kaplan-Meier curves showed significantly higher cardiovascular mortality rates in CKD patients whose serum magnesium levels were below 2.05 mg/dl. Conclusions: This observational cohort study showed that magnesium may be an independent predictor of future cardiovascular outcomes and is the first study demonstrating such a role in etiologically diagnosed CKD patients, across different stages.

Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children

Background and aim Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations of the MEFV gene. We analyse the impact of ethnic, environmental and genetic factors on the severity of disease presentation in a large international registry. Methods Demographic, genetic and clinical data from validated paediatric FMF patients enrolled in the Eurofever registry were analysed. Three subgroups were considered: (i) patients living in the eastern Mediterranean countries; (ii) patients with an eastern Mediterranean ancestry living in western Europe; (iii) Caucasian patients living in western European countries. A score for disease severity at presentation was elaborated. Results Since November 2009, 346 FMF paediatric patients were enrolled in the Eurofever registry. The genetic and demographic features (ethnicity, age of onset, age at diagnosis) were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. European patients had a lower frequency of the high penetrance M694V mutation and a significant delay of diagnosis (p<0.002). Patients living in eastern Mediterranean countries had a higher frequency of fever episodes/year and more frequent arthritis, pericarditis, chest pain, abdominal pain and vomiting compared to the other two groups. Multivariate analysis showed that the variables independently associated with severity of disease presentation were country of residence, presence of M694V mutation and positive family history. Conclusions Eastern Mediterranean FMF patients have a milder disease phenotype once they migrate to Europe, reflecting the effect of environment on the expression of a monogenic disease.

LDL-cholesterol lowering increases plasma apelin in isolated hypercholesterolemia

Apelin, a relatively newer adipokine with various actions in cardiovascular system, was recently reported to decrease in dyslipidemia. The present study addresses whether plasma apelin increases after hypolipidemic intervention either through therapeutic life style change (TLC) or statin treatment. A total of 134 patients were subjected to treatment with a TLC intervention for 12 weeks. Of these, 116 successfully completed the period, and LDL-cholesterol level decreased to target level (<160 mg/dL) in 54 (46.5%) individuals. The remaining 62 patients were treated with rosuvastatin for 12 weeks, and 56 of them finished the study. Circulating apelin, adiponectin, leptin, TNF-alpha, hsCRP and insulin levels were determined both at baseline and after TLC intervention and statin treatment. There was no significant change in plasma apelin concentration in patients unresponsive to TLC (p=0.110). LDL-cholesterol lowering either through TLC or statin treatment was accompanied by an increase in plasma apelin (p=0.000, p=0.020) and adiponectin (p=0.001, p=0.011). Serum leptin decreased after successful TLC (p=0.042/male, p=0.023/female) but not after statin treatment (p=0.959/male, p=0.134/female). Serum TNF-alpha (p=0.902) and plasma hsCRP (p=0.135) levels remained unchanged after TLC intervention but decreased after statin treatment (p=0.000, p=0.023, respectively). Plasma insulin and homeostasis model assessment scores decreased after TLC (p=0.000 for both) but not rosuvastatin treatment (p=0.865, p=0.722, respectively). In conclusion, independent of the type of treatment, reduction in LDL-cholesterol levels in otherwise healthy people with isolated dyslipidemia results in an increase in plasma apelin concentration. More experiments may show a substantial role for this peptide in the mechanism of atherosclerosis.

Evaluation of microhardness, surface roughness, and wear behavior of different types of resin composites polymerized with two different light sources

The microhardness, surface roughness and wear resistance of different types of resin composites, polymerized by a Quartz Tungsten Halogen (QTH) or Light Emitting Diode (LED) light curing units (LCU) were evaluated in this in vitro study. Cylindrical blocks were prepared from composites (8 mm in diameter, and 2 mm in thickness) and polymerized by a LED or a QTH LCU. Vickers hardness was measured on the top and bottom surfaces of the specimens. Surface roughness was measured with a surface profilometer on the top of the specimens. For the wear test, specimens were tested in a conventional pin-on-disc tribology machine under 15 N loads. The statistical analyses were performed by one-way analysis of variance (ANOVA) and t-tests, including the Bonferroni correction. Nanocomposite material Clearfil Majesty Posterior showed the highest hardness values in all polymerization types at the top and bottom surfaces (p < 0.05). Microhybrid Clearfil APX and hybrid Quixfil composites demonstrated the greatest surface roughness. Wear resistance of Clearfil Majesty Posterior was found to be the highest among the other tested resin composites. The results indicated that Clearfil Majesty Posterior demonstrated higher microhardness, less surface roughness, and higher wear resistance when compared with the other tested materials for both polymerization types.

Assessment of oxidative stress in the early posttransplant period: comparison of cyclosporine A and tacrolimus-based regimens.

Background: Oxidative stress is one of the leading causes of cardiovascular morbidity and mortality in chronic kidney disease. Although it is clear that many metabolic abnormalities improve, the effects of kidney transplantation on oxidative state are obscure. Methods: Twenty-three kidney transplant patients were included in the study. Eleven patients (mean age 27.9± 9.1 years) were treated with cyclosporine A (CsA) whereas 12 patients (mean age 22.4 ± 3.4 years) were treated with tacrolimus. Twenty-three healthy subjects served as controls. None of the patients or controls suffered from diabetes mellitus or an acute infection at the time of the study. Plasma malondialdehyde (MDA), plasma selenium (Se), erythrocyte glutathione peroxidase (GSH-Px), erythrocyte superoxide dismutase (SOD), erythrocyte Zn (EZn), and erythrocyte Cu (ECu) levels were studied before and in the 1st,3rd, 7th, 14th and 28th days after the transplantation. Results: The GSH-Px, SOD, ECu, EZn and selenium levels were lower and MDA levels were higher in patients than controls before transplantation (p < 0.001 for all). MDA levels decreased and SOD, GSH-Px, ECu, EZn levels increased in parallel to the decrement of serum creatinine levels following the renal transplantation. No difference was found among the patients regarding the treatment regime. Conclusion: The study data suggest that the improvement in oxidative state parameters begins at the first day of renal transplantation and continues at the 28th posttransplant day in living donor transplantations.

Blockade of the renin-angiotensin system increases plasma adiponectin levels in type-2 diabetic patients with proteinuria.

Background/Aims: Adiponectin seems to be an important modulator for metabolic and vascular diseases. A case study was designed to measure plasma adiponectin levels and to investigate the effects of angiotensin-converting enzyme inhibitors on adiponectin levels in type-2 diabetic patients with proteinuria. Methods: Forty-nine patients (28 males, 21 females) and 23 healthy volunteers (13 males, 10 females) were included in the case study. Patients with proteinuria were treated with 5 mg/day ramipril (n = 21) for 4 weeks. Results: Adiponectin levels of patients were significantly lower than those of healthy volunteers (p < 0.001). There were significant negative correlations between adiponectin concentrations and insulin levels as well as the homeostasis model assessment (HOMA) index in the patient group (r = –0.655, p < 0.001; r = –0.469, p = 0.001, respectively). There was also a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r = –0.912, p < 0.001). Plasma adiponectin levels in patients with proteinuria (n = 21; 4.81 ± 3.17 µg/ml) were significantly lower than those without proteinuria (n = 28; 10.25 ± 2.03 µg/ml; p < 0.001). After the treatment period, adiponectin levels significantly increased (p < 0.001) and proteinuria, plasma insulin, and HOMA indexes significantly decreased in the treatment group (p < 0.001, p < 0.001, p = 0.002, respectively). Conclusions: The results suggest that adiponectin is inversely correlated with proteinuria and treatment with ramipril both corrects proteinuria and increases the low adiponectin levels in diabetic patients.

Optimal strategy for penile rehabilitation after robot‐assisted radical prostatectomy based on preoperative erectile function

Removing of prostate for the treatment of localized prostate cancer is associated with a variable loss of erectile function due to injury of the nerves of erection during operation. Some researchers have reported that after nerve‐sparing radical prostatectomy (RP), the natural recovery time of erectile function is at least 2 years. Factors such as thermal damage, ischaemic injury, mechanically induced nerve stretching and the local inflammatory effects of surgical trauma may also impair the cavernous nerves during RP. The concept of penile rehabilitation was first studied by Montorsi et al. in 1997. They showed that the use of any drug or device at or after RP could maximize the recovery of erectile function. Penile rehabilitation programmes (PRPs) with vasoactive agents, such as oral phosphodiesterase‐5 inhibitors (PDE5Is), intraurethral and intracavernosal vasoactive agents, and vacuum erection devices (VEDs) can protect erectile tissue integrity and prevent corporal smooth muscle atrophy and diminish collagen formation. The present findings are consistent with previous reports that PRPs have a significant beneficial effect on early erectile function recovery and that preoperative erectile function is one of the important predictors of erectile function after RP. Patients can be referred for penile rehabilitation if they have any degree of erectile function (mild, moderate or normal) before operation. We also showed that the combination of PDE5Is and VEDs for PRPs offers the shortest erectile function recovery period.