Efficacy of statins on sirtuin 1 and endothelial nitric oxide synthase expression: the role of sirtuin 1 gene variants in human coronary atherosclerosis

Statins are 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors and are used to reduce the risk of coronary artery disease (CAD) due to their pleiotropic effects. Recently, greater focus has been placed on the role of sirtuin 1 (SIRT1) in cardiovascular disease research. However, insufficient data exist on the relationships between statins, SIRT1 protein levels, and SIRT1 gene variants. In the present study, we investigated the effects of statins, atorvastatin and rosuvastatin, in CAD patients by analysing the associations between SIRT1 gene variants, rs7069102C>G and rs2273773C>T, and SIRT1/endothelial nitric oxide (eNOS) expression, as well as total antioxidant and oxidant status, and the oxidative stress index. SIRT1 expression was significantly higher, and eNOS expression was significantly lower in CAD patients when compared with controls. Statin treatment reduced SIRT1 expression and increased eNOS expression, similar to the levels found in the control population, independent from the studied SIRT1 gene variants. Oxidative stress parameters were significantly increased in CAD patients, and were decreased by statin treatment, demonstrating the antioxidative effects of statins on atherosclerosis. These results indicate that statin treatment could produce its protective effect on cardiovascular disease through the inhibition of SIRT1 expression. This is the first study reporting on the effect of statins, specifically atorvastatin and rosuvastatin, on SIRT1 expression in CAD patients.     

The effect of antihypertensive therapy on dry eye disease

Context: There is a generalization that “antihypertensive (antiHT) therapy causes Dry Eye Syndrome”, which has been claimed for years however most of the publications are epidemiological studies. We performed a clinical study to investigate the effects of antiHT agents on tear function.

Objective: The aim of this article is to evaluate the effects of different classes of antiHT medications on tear osmolarity, ocular surface problems and dry eye symptoms.

Materials and methods: Prospective, non-randomized a clinical study. A total of 71 patients who would be initiated antiHT medication due to elevated systemic blood pressure were included in the study. Thirty of these patients were given antiHT drugs containing diuretic (diuretic +), and 41 of them were given diuretic-free drugs (diuretic ?). While the number of the patients medicated in the group that received Angiotensin Converting Enzyme inhibitors (ACE inh)/Angiotensin receptor blockers (ARB) (ACE/ARB +) was 29, the number of those medicated in the ACE/ARB-free group (ACE/ARB ?) was 42. Ocular surface disease index scores, tear osmolarity, Schirmer I test, tear film break-up time (TBUT), fluorescein (FL) and rose bengal corneal staining patterns of the patients were analyzed. The patients were examined through the repetition of all the tests in the 1st and the 3rd month.

Results: The participants (n?=?71) comprised 38 males and 33 females with a mean age of 51.8?±?10.4. When the first (0–1st month) and the third month (0–3rd months) control measurements between diuretics (+) and diuretics (?) groups before and after antiHT therapies were compared, a statistically significant difference was not found in any of the tests applied. When the 0–1st month measurements of ACE/ARB (+) and ACE/ARB (?) groups were compared, it was observed that staining with FL in ACE/ARB (+) group decreased in a statistically significant manner (p?=?0.035) and there was a significant increase in TBUT values (p?=?0.022).

Discussion and conclusion: The use of antiHT drugs containing diuretic had no adverse effect on the tear function tests, but using drugs that contain ACE/ARB could have a positive impact.     

Diagnostic value of integrated ultrasonic backscatter in congestive cardiomyopathy.

Congestive cardiomyopathy is a fatal myocardial disease which can be diagnosed by clinical findings, electrocardiography, roentgenography and echocardiography. Tissue characterization and pathology have been determined recently using histogram methods to analyze ultrasonographs. In this study ultrasonic backscatter analysis for differentiation of normal and diseased myocardium was tested. Two-dimensional echo data and radio frequency signals of long-axis views of the left ventricular posterior wall of 10 healthy children and 14 patients with congestive cardiomyopathy in systolic and diastolic phase were digitized online into the computer memory. Cyclic variation was obtained in the control group but no variation was detectable in myopathic hearts.     

Lycopene and resveratrol improve post‐thaw bull sperm parameters: sperm motility,mitochondrial activity and DNA integrity

We focussed on evaluating the protective effect of lycopene and resveratrol on post‐thaw bull sperm and oxidative stress parameters. Nine ejaculates for each bull were used in the study. Each ejaculate, splitted into three equal aliquots and diluted at 37 °C with base extenders containing lycopene (1 × 10^?3 g ml^?1) and resveratrol (1 mm ), and no antioxidant (control), was cooled to 5 °C and then frozen. Frozen straws were thawed in a water bath for evaluation. The supplementation of the semen extender with lycopene and resveratrol increased the percentages of post‐thawed computer‐assisted sperm analysis (CASA) motility (55.8 ± 3.8 and 61.9 ± 4.0%) and progressive motility (38 ± 2.4 and 37 ± 8.8), compared with the controls (50.7 ± 2.65 and 33.3 ± 3.74%, respectively, P < 0.05). Resveratrol provided a higher ALH (4.3 ± 0.1), in comparison with the control (3.9 ± 0.3, P < 0.05). The supplementation of the semen extender with lycopene and resveratrol produced a higher mitochondrial activity (24.6 ± 2.9 and 30.1 ± 6.5% respectively), compared with that of the control (11.8 ± 9.5%, P < 0.05). It was determined that both antioxidants resulted in a lower percentage of sperm with damaged DNA than that of the control (P < 0.05). Sperm motion characteristics except for ALH, acrosome integrity, sperm viability and oxidative stress parameters were not affected by the adding of lycopene and resveratrol.     

Effect of Cold Application and Tizanidine on Clonus: Clinical and Electrophysiological Assessment

Background/Objectives: Clonus is an involuntary rhythmic muscle contraction after sudden muscle stretch that occurs as a result of a lesion in the upper motor neurons. The real mechanism behind clonus remains obscure. The objective of this study was to investigate the effects of central-acting tizanidine treatment and peripheral extremity cooling on clonus.

Participants: Thirty-eight patients with upper motor neuron involvement and sustained clonus.

Methods: The 38 patients were divided into 3 groups: cold group (n = 19), tizanidine group (n = 13), and patient control group (n = 6). A separate group of 21 able-bodied volunteers served as controls for the cold group. The physiologic effects of cold application were measured in the able-bodied group and compared with the effects in the patients in the cold group. All participants were evaluated by clinical and electrophysiologic measurements.

Results: Changes in clinical and electrophysiologic measurements in the cold group were statistically significant compared with those of the tizanidine and patient control groups.

Conclusions: Subsequent and long-term cold application induced prolonged inhibitory effects on clonus. Tizanidine had no significant effect on clonus. Suppression of clonus by cold highlights the importance of peripheral input in relation to central mechanisms.     

Investigation of the Effect of Milrinone on Renal Damage in an Experimental Non-Heart Beating Donor Model

ABSTRACT

Purpose: In our study, it was aimed to investigate the preventive effect of milrinone on renal damage in experimental controlled non-heart-beating donors (NHBDs) model. Materials and Methods: Sixteen rats randomly divided into 2 groups, 8 rats in each were used. Group 1 was control, group 2 was milrinone group. Group 1 rats received 1.25 ml 0.09% NaCl intraperitoneally equivalent to the milrinone diluted volume. Group 2 rats were administered intraperitoneally with 0.5 mg/kg of milrinone 2 hours before cardiac arrest. After the cardiac arrest, left nephrectomy was applied to the rats. Malondialdehyde, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) activities, Caspase-3 (apoptotic index) and histopathological evaluation were performed in the tissues. Results: In the milrinone group, the total injury score was significantly lower relative to the control group (p = 0.001). Caspase-3 staining was moderately strong in the control group but weaker in the milrinone group. Apoptotic index was significantly lower in the milrinone group compared to the control group (p = 0.001). In comparison between groups, SOD and GPx in the milrinone group was significantly higher than the control group (p = 0.008, p = 0.006). Conclusions: Milrinone has been shown to be effective in the prevention of tissue damage due to oxidative stress and inflammatory process in the renal of warm ischemia in the experimental NHBDs model and in protecting the renal. Milrinone increases antioxidant activity while reducing apoptosis. Systemic administration of milrinone prior to cardiac arrest may be beneficial. Administration of milrinone to the recipient in the perioperative period may contribute to donor function.     

Effect of Intravenous Iron Sucrose on Oxidative Stress in Peritoneal Dialysis Patients

Aim. Intravenous iron therapy is an accepted treatment for patients receiving hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Studies have found enhanced oxidative stress in hemodialysis patients receiving intravenous iron, but there are no clinical data for CAPD patients. The aim of the current study was to investigate the effect of 100 mg of intravenous iron-sucrose on the erythrocyte (RBC) antioxidant enzymes (namely, superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSHPx]) and plasma malondialdehyde (MDA), an oxidant molecule, in CAPD patients. Methods. Twelve CAPD patients receiving maintenance intravenous iron-sucrose were recruited. After a 12-hour fast, blood samples were taken for hemoglobin, iron, ferritin, and high-sensitivity C-reactive protein (hsCRP), and for baseline activities of erythrocyte antioxidant enzymes (i.e., SOD, CAT, GSHPx) and the plasma oxidant molecule, MDA. 100 mg iron-sucrose was infused over 30 minutes. Blood samples taken during (i.e., 15 minutes after commencement of infusion) and after (i.e., at 30 minutes, 60 minutes, and 6 hours after commencement) the infusion were taken for measurement of plasma iron, ferritin, TSAT, RBC SOD, CAT, GSHPx, and plasma MDA. Results. Plasma iron and transferrin saturation elevated significantly during infusion (p < 0.05). There was no significant change in erythrocyte SOD, CAT, GSHPx, or in MDA activities. There was a reduction of GSHPx activity at the 30th minute (from 153.69 ± 66.69 to 123.68 ± 25.50 mU/mL), but it was not statistically significant. The patients were grouped according to baseline ferritin (100–400 and 400–800 ng/mL); 60th-minute MDA was significantly higher in the latter group (p < 0.05). There was no correlation between hsCRP and oxidant-antioxidant balance. No correlation was noted between RBC antioxidant enzymes or plasma oxidant molecule and ferritin levels. Conclusion. There are no acute deteriorating effects from a 100 mg of intravenous iron-sucrose in CAPD patients with optimal iron stores. This dose may be applied safely in CAPD patients.