Ahmet Musmul

Chitosan and blueberry treatment induces arginase activity and inhibits nitric oxide production during acetaminophen-induced hepatotoxicity

Background: Liver diseases have become a major problem of the worldwide. More than 50% of all cases of liver failure can be attributed to drugs. Among these, acetaminophen is the most common cause. Objective: The aim of this study was to investigate the the hepatoprotective effects of blueberry and chitosan on tissue arginase activity, ornithine and nitric oxide levels during the acetaminophen-induced hepatotoxicity. Materials and Methods: Acetaminophen (250 mg/kg body weight per day), blueberry (60 mg/kg body weight per day) and, chitosan (200 mg/kg body weight per day) were administered to the rats by oral gavage during the experimental period. Results: Blueberry and chitosan significantly decreased liver arginase activity and ornithine levelsand and increased nitric oxide levels. Glutathione levels were remarkably increased by chitosan and blueberry treatments. Conclusion: The results of the present study indicate that blueberry and chitosan effectively protected against the acetaminophen-induced hepatotoxicity. The hepatoprotective effect afforded by blueberry and chitosan can be attributed to its antioxidant and anti-inflammatory activities.

Acute and subacute effects of EV iron sucrose on endothelial functions in hemodialysis patients.

Background: Iron support is an important component of treatment of anemia in hemodialysis (HD) patients. However, there are concerns about endovenous (EV) iron therapy that may cause endothelial dysfunction (ED) by increasing oxidative stress (OS) and lead to cardiovascular events. In this study, we aimed to evaluate the effects of high and repeated doses of EV iron sucrose on endothelial functions in acute and subacute phases. Methods: We included 15 HD patients to our study. There were 16 patients with iron deficiency but normal kidney functions in control group. We also evaluated endothelium-dependent vasodilatation (EDV) and nitroglycerin-induced vasodilatation (NIV) from the brachial artery by ultrasonography at the beginning of the study, and then 200 mg EV iron sucrose was given initially to both groups for 1 h in 250 cc 0.9% saline and 4 h after the end of the infusion (acute phase) sonographic vasodilatation parameters were measured from brachial artery. These measurements and laboratory tests were repeated 1 week after the end of a total 1000 mg EV iron sucrose replacement (200 mg/week). Results: There was a statistically significant increase in hemoglobin and ferritin levels after the EV iron sucrose therapy in both control and patient groups. EDV values in the HD group were significantly lower than that in the control group before therapy (6.25% vs. 10.53%, p < 0.05). EV iron sucrose therapy did not alter EDV and NIV values at the 4th hour and 6th week in both control and patient groups. Conclusion: According to our study, compared with the control group with normal kidney functions, HD patients had impaired endothelial functions. However, in HD patients, high and repeated doses of EV iron sucrose do not have deleterious effects on endothelial functions at acute and subacute phases and can be used safely in that patient group.

Peripheral blood regulatory T cell levels are correlated with some poor prognostic markers in newly diagnosed lymphoma patients.

Regulatory T cells (Tregs) are a specialized subpopulation of CD4+ T cells which maintain the immune system homeostasis. They may increase during cancer progression and have been correlated with a worse prognosis in many malignancies. However, the role of Treg cells in lymphoma is debated.

Echocardiographic evaluation of epicardial adipose tissue in non-diabetic, non-hypertensive hemodialysis patients.

Abstract Purpose: It has been found out that the epicardial adipose tissue (EAT) measured by echocardiography is related with various metabolic parameters. Being accepted as the new cardiovascular risk indicator, there have been few studies on EAT in relation to the patients with end-stage renal failure. In our study, we aim to evaluate EAT and carotid intima media thickness (CIMT) in non-diabetic, non-hypertensive hemodialysis (HD) patients. Methods: Our study recruited 47 non-diabetic, non-hypertensive HD patients (22 males, 25 females, median age 54 (44.3–60.8) years) and an age-gender matched control group consisting 41 healthy subjects (17 males, 24 females, median age 52 (48–56) years). In all patients, EAT was measured by echocardiography and CIMT by ultrasonography; and routine laboratory parameters were studied. Results: In our study, we obtained laboratory findings matching with the profiles of uremic patients among HD patients and CIMT values of HD patients are significantly higher than that of the control group [0.79 (0.64–0.93) vs. 0.6 (0.53–0.68) p < 0.001], and EAT values are similar [0.5 (0.33–0.6) vs. 0.4 (0.4–0.53) p > 0.05]. Conclusions: EAT is not a cardiovascular risk indicator in HD patients without diabetes mellitus and hypertension. Besides, echocardiographic measurement of EAT is easy, non-invasive, cheap and credible method.

Late Effects of Renal Transplantation on Endothelial Functions and Cardiac Morphology

BACKGROUND Endothelial dysfunction is common in patients undergoing hemodialysis (HD), and cardiovascular morbidity and mortality are higher in these patients. In this study, we evaluated the late posttransplantation effects of cyclosporine and tacrolimus on endothelial function, inflammation, and cardiac architecture. METHODS The study included 12 patients undergoing hemodialysis (group 1); 22 renal transplant recipients, of which 13 were receiving cyclosporine therapy (group 2) and 9 were receiving tacrolimus therapy (group 3); and 12 healthy control individuals (group 4). Kidney recipients were included if the transplantation procedure had been performed at least 1 year before the study. Asymmetric dimethylarginine, C-reactive protein, carotid intima-media thickness, left ventricular posterior wall thickness, interventricular septal thickness, left ventricular muscle mass index, flow-mediated dilation, and nitroglycerine-induced dilation of the brachial artery were evaluated. RESULTS Serum asymmetric dimethylarginine, C-reactive protein, carotid intima-media thickness, left ventricular posterior wall thickness, interventricular septal thickness, and left ventricular muscle mass index values were significantly higher in patients undergoing HD than in the other 3 groups (P < .05), whereas percent change in flow-mediated dilation and nitroglycerine-induced dilation of the brachial artery was significantly lower (P < .05). CONCLUSION Patients undergoing HD demonstrate endothelial dysfunction. In the late posttransplantation period, kidney recipients seem to have similar endothelial function and cardiac architecture as in the healthy population. This result may explain the reduction in cardiovascular morbidity and mortality after transplantation in patients undergoing HD. Tacrolimus and cyclosporine have similar effects on endothelial function.

Comparison of the Effects of Levosimendan Dobutamine and Vasodilator Therapy on Ongoing Myocardial Injury in Acute Decompensated Heart Failure.

Background: Cardiac troponins (cTn) are reliable and the most sensitive biomarker in the setting of acute decompensated heart failure (ADHF). Acute decompensated heart failure is usually associated with worsening chronic heart failure, and it may be caused by ongoing minor myocardial cell damage that may occur without any reported precipitating factors. Methods: We compared the short-term effect of levosimendan (LEV), dobutamine (DOB), and vasodilator treatment (nitroglycerin [NTG]) on myocardial injury with hemodynamic, neurohumoral, and inflammatory indicators. One hundred twenty-two patients with a mean age of 66 ± 9 years were treated with LEV (n = 40), DOB (n = 42), and NTG (n = 40) and examined retrospectively. Blood samples (cTnI, N-terminal probrain natriuretic peptide [NT-proBNP], highly sensitive C-reactive protein [HsCRP], and others), left ventricular ejection fraction (LVEF), systolic pulmonary artery pressure (sPAP), and 6-minute walk distance (6MWD) were compared before and after treatment. Results: At admission, detectable levels of cTnI were observed in 53% of patients (≥0.05 ng/mL). Serial changes in the mean cTnI levels were not significantly different between the groups (LEV 0.04 ± 0.01 to 0.03 ± 0.01 ng/mL; DOB 0.145 ± 0.08 to 0.08 ± 0.03 ng/mL; NTG 0.1 ± 0.03 to 0.09 ± 0.02 ng/mL; overall P = .859). Favourable effects on the NT-proBNP, sPAP values, LVEF, 6MWD, and HsCRP were observed overall, especially in the LEV groups. Conclusion: Beneficial effects of short-term use of LEV, DOB, and NTG on ongoing myocardial injury were demonstrated. These findings can be attributed to the anti-ischemic properties as well as the hemodynamic, neurohumoral, and functional benefits from the positive inotropes, especially LEV, in patients with ADHF.

Matrix metalloproteinases are possible targets in monocrotaline-induced pulmonary hypertension: investigation of anti-remodeling effects of alagebrium and everolimus.

Objective: In our study, sildenafil alone and everolimus or alagebrium in combination with sildenafil were investigated in terms of their additional therapeutic and anti-remodeling activity in monocrotaline-induced pulmonary hypertension (PH) model in rats. In particular, the inter-relationships between PH and matrix metalloproteinases (MMPs) were investigated. Methods: The pulmonary artery responses of male Sprague Dawley rats were recorded using myography, and the quantities and activities of MMPs were analyzed in homogenates of the pulmonary arteries and lungs by enzyme-linked immunosorbent assays, activity assays, and gelatin zymography techniques. Results: Our results indicated that the therapeutic effects of sildenafil were accompanied by its suppressor effects on MMP activity. It was also shown that everolimus or alagebrium in combination with sildenafil showed additional regulatory effects on MMPs as well as functional responses on pulmonary artery pressure. Therefore, the enzymes in the MMP superfamily are likely to be target molecules for the treatment of PH. Conclusion: In conclusion, MMPs were involved in the pathogenesis of PH, and our results suggested that the addition of everolimus or alagebrium to sildenafil therapy may be beneficial in PH. Our results indicated that agents that limit pulmonary vascular hypertrophy and inflammation via their anti-remodeling effects significantly ameliorate mortality and morbidity in PH.

Pseudoexfoliation syndrome in chronic kidney disease patients.

Abstract This study was performed to determine whether chronic kidney disease (CKD) is associated with an increased risk of pseudoexfoliation (PEX) syndrome. This is an age-matched case control study evaluating frequency of PEX in patients over age 40 with the diagnosis of stage 1–4 CKD and those undergoing hemodialysis (HD). Subjects over age 40 with hypertension and/or diabetes mellitus (DM) and normal kidney functions were studied as a control group. CKD was diagnosed as decreased glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m2 for at least 3 months. Study groups were arranged as group 1 consisting of HD receiving CKD patients, group 2 consisting of CKD patients who do not need HD and group 3 as a control. Demographic properties and the prevalence of PEX were evaluated and compared between groups. Because of the effect of DM on PEX occurrence, it was also evaluated after exclusion of diabetic patients. A total of 101 cases in group 1, 106 cases in group 2 and 117 cases in group 3 were included in the study. Pseudoexfoliation was found in 7 (6.9%) patients in group 1, 5 (4.7%) patients in group 2 and 7 (5.9%) patients in group 3 (p > 0.05). After exclusion of diabetic patients the prevalence of PEX changed as 4 (5.6%) in group 1, 2 (4.4%) in group 2 and 1 (1.8%) in group 3 (p > 0.05). In conclusion, CKD was not associated with increased prevalence of PEX in this study.

Assessment of genetic risk factors for thromboembolic complications in adults with idiopathic nephrotic syndrome.

AIMS Nephrotic syndrome (NS) may occur with acquired hypercoagulability, however, the fact that it is accompanied by an underlying hereditary thrombophilia, especially combined hereditary thrombophilia would lead to thrombotic events. In this study, we aimed to evaluate the contribution of genetic thrombophilia to development of thrombotic events in adult patients with NS. MATERIAL AND METHODS Factor V Leiden (FVL), prothrombin, and methylenetetrahydrofolate reductase (MTHFR) gene mutation were studied in 51 newly diagnosed idiopathic NS patients and age- and gender-matched 20 healthy control subjects included in the study. Renal vein Doppler ultrasound was conducted in order to investigate the prevalence of subclinical renal vein thrombosis. RESULTS Of 51 patients, 6 (11.8%) were established to have thromboembolic (TE) complications at the time of diagnosis (4 symptomatic, 2 subclinical), and no recurring thrombotic episode was observed. Genetic mutation was established in all patients that were found to have TE complications. Acquired hypercoagulability factors were similar in patients without and with TE complication. CONCLUSIONS The coexistence of inherited thrombophilia in NS may facilitate thromboembolic complications. If the cause of thrombosis cannot be explained by the usual factors attributed to the occurrence of thrombosis in NS, screening for the other factors, such as FVL, MTHFR, and prothrombin gene mutation, may be beneficial.

L-Cysteine Partially Protects Against Acrylamide-Induced Testicular Toxicity

Background: Acrylamide is a widespread substance with many areas of utilization. Acrylamide also forms a part of high-temperature-processed starchy foods. To date, numerous in vivo and in vitro studies have documented that acrylamide poses toxic effects on various organ systems. Aims: To determine the potential protective effect of L-cysteine on acrylamide-induced testicular toxicity. Study Design: Animal experimentation. Methods: We randomly divided 28 rats into four groups: control (0.9% saline), L-cysteine (150 mg/kg), acrylamide (40 mg/kg), and acrylamide+L-cysteine. After a 10-day intraperitoneal injection period, we euthanized the animals, recorded their body and testis weights, collected blood samples for serum testosterone measurement, and excised the testes for histopathological and morphometric evaluation. Immunohistochemical scoring of proliferating cell nuclear antigen and bax proteins was performed. Results: Acrylamide reduced body (p<0.01) and testis weights (p<0.05), seminiferous tubule diameter (p<0.001), and proliferating cell nuclear antigen expression (p<0.05) but increased bax protein expression (p<0.01) and the percentage of seminiferous tubules containing multinucleated giant cells (p<0.001). However, no significant change was observed in serum testosterone level of the experimental groups when compared with that of controls. L-cysteine administered with acrylamide decreased multinucleated giant cell number (p<0.001) and reversed the reduced proliferating cell nuclear antigen positivity (p<0.001) but showed no effect in restoring other parameters compared with the group treated with acrylamide alone. Conclusion: Considering the dose and duration employed, the present study concluded that L-cysteine partially protects testis against acrylamide-induced toxic effects.