The Relationship between the MEFV Genotype,Clinical Features,and Cytokine-Inflammatory Activities in Patients with Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by periodic attacks of fever and polyserositis. The effects of the MEFV genotype differences on clinical picture and inflammatory activity have not been well documented. The aim of this study was to investigate levels of conventional inflammation markers, procalcitonin, interleukin levels, TNF-alpha, and C5a levels in patients with FMF who had different MEFV genotypes and compare them with those of healthy subjects. The study consisted of 41 patients with FMF (F/M: 23/18), and 31 healthy subjects (F/M: 18/13). Tests were performed during the attack-free period.

White-blood cell count, CRP and IL-8 levels were higher in patients with FMF than in healthy subjects (p < 0.05) and also higher in M680I carriers than in the patients with M694V allele carriers. However, ESR, fibrinogen, procalcitonin, IL-6, C5a, TNF-alpha, and IgD levels were not significantly different between patients and healthy subjects (p > 0.05). Arthralgia or arthritis was significantly higher in M694V carriers than in non-M694V carriers (p < 0.05). It is concluded that the clinical features and inflammatory-cytokine activities were higher in patients with FMF during the attack-free period than in healthy subjects, and the different genotype might be related to different clinical pictures.     

Effects of Rosiglitazone on Cardiac Function in CAPD Patients: A Tissue Doppler Study

Background. Insulin resistance was an independent predictor of cardiovascular mortality in uremic patients without diabetes. Rosiglitazone (ROS) improves insulin sensitivity in the liver, muscle, and adipose tissue. We prospectively investigated the effects of ROS on cardiac functions by standard (SDE) and tissue Doppler echocardiography (TDI) in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods. A total of 24 CAPD patients (13 males, 11 females; mean age 42.2 ± 14.8 years) were included. Routine blood samples were examined. Left and right ventricular functions were assessed, and myocardial performance index (MPI) was calculated by SDE and TDI at baseline and after 12-month ROS therapy. Left and right atrial volumes were measured and indexed to body surface area. Results. When compared with baseline, after 12 months of ROS treatment, it was shown that early (E) and late (A) diastolic velocities of atrioventricular valves, E/A ratio, mitral E-wave deceleration time (DT), isovolumetric relaxation time (IVRT), and MPI were similar (p > 0.05). Also, no significant changes were detected in LV dimensions, LV mass index, LVEF, LA volume index, or RA volume index measured by SDE before and after ROS therapy (p > 0.05). Left and right ventricular function parameters measured by TDI including Sm, Em, Am, Em/Am ratio, E/Em ratio, and MPI were similar. Conclusion. It was found that there was no negative effect of long-term ROS therapy on cardiac functions measured by SDE and TDI in CAPD patients.     

Effects of Low Sodium Dialysate in Chronic Hemodialysis Patients: An Echocardiographic Study

Background. Chronic kidney disease (CKD) and hemodialysis (HD) patients who cannot restrict sodium consumption in their diets sometimes develop significant saline excess and hypertension between dialyses. This study assessed the effect of relatively low sodium dialysate dialysis on changes of echocardiography in hemodialysis patients. Methods and Results. Eighteen patients with end stage renal failure on chronic HD were studied (8 females, 10 males) with a mean age 48.3 ± 14.6 (24–70) years. The mean time on HD was 30.8 ± 14.0 (12–60) months. Patients with hematocrit levels under 24% were excluded from the study. In all patients, echocardiography was performed thrice weekly before and after eight-week HD treatment with low sodium dialysate hemodialysis by the same operator (135 mEq/L for patients with sodium levels less than 137, 137 for patients with sodium levels over 137). Left atrium (LA) and left ventricle (LV) volumes and ejection fractions were measured, specifically: LV systolic diameter (LVSD), LV diastolic diameter (LVDD), interventricular septum (IVS), tricuspid regurgitation (TR), mitral regurgitation (MR), pulmonary artery pressure (PAP), and inferior vein cava diameter (IVCD). Results. In terms of echocardiographic parameters, LVSD, TR, PAP, and IVCD were statistically decreased after low-sodium dialysate treatments (p?=?0.002, 0.04, 0.013, and 0.00, respectively). Predialysis systolic and diastolic blood pressure (BP), post-dialysis systolic blood pressure, and interdialytic weight gain was statistically decreased when compared to basal levels (p?=?0.00, p?=?0.011, p?=?0.022, p?=?0.001, respectively). Conclusion A reduction of the dialysate sodium concentration based on the predialysis sodium levels of the patients could reduce the systolic BP and decrease the volume load on the heart as assessed by echocardiography. Within this short period, postdialysis diastolic BP could not be lowered. The effect of this approach should be studied in broad and lengthy series.     

New nanodrug design for cancer therapy: Its synthesis,formulation, in vitro and in silico evaluations

The aim of this study was to develop a novel nanosize drug candidate for cancer therapy. For this purpose, (S)-methyl 2-[(7-hydroxy-2-oxo-4-phenyl-2H-chromen-8-yl)methyleneamino]-3-(1H-indol-3-yl)propanoate (ND3) was synthesized by the condensation reaction of 8-formyl-7-hydroxy-4-phenylcoumarin with l -tryptophan methyl ester. Its controlled release formulation was prepared and characterized by different spectroscopic and imaging methods. The cytotoxic effects of ND3 and its controlled release formulation were evaluated against MCF-7 and A549 cancer cell lines, and it was found that both of them have a toxic effect on cancer cells. For drug design and process development, the molecular docking analysis technique helps to clarify the effects of some DNA-targeted anticancer drugs to determine the interaction mechanisms of these drugs on DNA in a shorter time and at a lower cost. By using the molecular docking analysis and DNA binding assays, the interaction between the synthesized compound and DNA was elucidated and non-binding interactions were also determined. To predict the pharmacokinetics, and thereby accelerate drug discovery, the absorption, distribution, metabolism, excretion and toxicity values of the synthesized compound were determined by in silico methods.     

Serum indoleamine 2,3 dioxygenase and tryptophan and kynurenine ratio using the UPLC-MS/MS method,in patients undergoing peritoneal dialysis,hemodialysis, and kidney transplantation

Background: The level and activity of indoleamine 2,3-dioxygenase (IDO) and the concentrations of L-tryptophan and its metabolite L-kynurenine were determined in association with various renal diseases. However, there have been no data regarding these parameters in patients on peritoneal dialysis compared to those undergoing hemodialysis or kidney transplantation.

Methods: This study investigated the level and activity of IDO and determined oxidative balance by calculating the total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI). We enrolled 60 kidney disease patients, including 20 on peritoneal dialysis (PD group), 19 on hemodialysis (HD group), and 21 with kidney transplantation (KT group), as well as 21 control group.

Results: IDO levels were increased in the PD, HD, and KT groups compared to the control group. The concentration of kynurenine was significantly increased in the PD group compared to the other groups (p?p?p?Conclusion: The results showed that IDO levels were increased in peritoneal dialysis and hemodialysis patients and in renal transplant recipients, while oxidative stress was found to be related to IDO activity and was most increased in the patients on peritoneal dialysis.