Strict heart rate control attenuates prothrombotic state and platelet activity in patients with non-valvular permanent atrial fibrillation.

BACKGROUND: The underlying mechanisms of increased risk of thrombo-embolism in atrial fibrillation (AF) are not completely understood; however, substantial evidence supports that AF is associated with a prothrombotic state. Accordingly, we hypothesized that strict rate control could attenuate platelet activity and thrombotic state in patients with non-valvular AF. METHODS: Seventy-five patients with non-valvular AF were divided into 2 groups based on heart rate: (1) normal ventricular rate (n = 34, 18 female) and (2) high ventricular rate (n = 39). Thirty-three sex- and age-matched subjects in sinus rhythm were included as control. Thirty patients with high ventricular rate (16 female) were successfully followed. Markers of platelet function were measured at baseline and repeated 1-month after adequate rate control in high ventricular rate group. RESULTS: Serum fibrinogen levels were significantly higher in AF patients with high ventricular rate than that in controls. Mean platelet volume, soluble CD40L and ß-Thromboglobulin were significantly higher in AF patients with high ventricular rate than those in both AF patients with normal ventricular rate and controls. Soluble CD40L and ß-Thromboglobulin were significantly higher in AF patients with normal ventricular rate than those in controls. One-month after adequate rate control, serum fibrinogen, soluble CD40L and ß-Thromboglobulin levels significantly decreased (from 2.26 ± 1.02, 85.01 ± 37.05, 3.10 ± 0.90 to 1.55 ± 1.08, 66.34 ± 33.72, 2.71 ± 0.53; p < 0.001, p = 0.002, p = 0.03, respectively) in high ventricular rate group. CONCLUSIONS: AF patients with high ventricular rate had increased indices of platelet activity and thrombotic state. Furthermore, strict rate control significantly decreased indices of thrombotic state and platelet activity in those patients.

Effects of maternally exposed coloring food additives on receptor expressions related to learning and memory in rats.

Exposure to artificial food colors and additives (AFCAs) has been implicated in the induction and severity of some childhood behavioral and learning disabilities. N-methyl-D-aspartate receptors (NMDARs) and nicotinic acetylcholine receptors (nACHRs) are thought to be effective in the learning and memory-generating process. In this study, we investigated the effects of intrauterine exposure to AFCAs on subunit concentrations of NMDARs and nAChRs isoforms in rats. We administered a mixture of AFCAs (Eritrosin, Ponceau 4R, Allura Red AC, Sunset Yellow FCF, Tartrazin, Amaranth, Brilliant Blue, Azorubin and Indigotin) to female rats before and during gestation. The concentration of NR2A and NR2B subunits and nAChR α7, α4ß2 isoforms in their offspring's hippocampi were measured by Western Blotting. Expressions of NR2B and nAChR ß2 were significantly increased (17% and 6.70%, respectively), whereas expression of nAChR α4 was significantly decreased (5.67%) in male experimental group compared to the male control group (p<0.05). In the female experimental group, AFCAs caused a 14% decrease in NR2B expression when compared to the female control group (p<0.05). Our results indicate that exposure to AFCAs during the fetal period may lead to alterations in expressions of NMDARs and nAChRs in adulthood. These alterations were different between male and female genders.

Effects of maternally exposed colouring food additives on cognitive performance in rats.

Artificial food colourings and additives (AFCAs) have long been suggested to adversely affect the learning and behaviour in children. In this study, we aimed to provide additional data to clarify the possible side effects of colouring additives on behaviour and memory. We administered acceptable daily intake values of AFCAs as a mixture (Eritrosin, Ponceau 4R, Allura Red AC, Sunset Yellow FCF, Tartrazin, Amaranth, Brilliant Blue, Azorubin and Indigotin) to female rats before and during gestation and then tested their effects on behaviour and on spatial working memory in their offspring. Effects on spatial learning and memory were evaluated by Morris water maze, behavioural effects were evaluated by open-field test and forced swim test. Our results showed that commonly used artificial food colourings have no adverse effects on spatial working memory and did not create a depressive behaviour in offspring. But they showed a few significant effects on locomotor activity as AFCAs increased some parameters of locomotor activity.

Plasma lipoprotein(a) levels in patients with slow coronary flow.

INTRODUCTION: Slow coronary flow (SCF) is a microvascular disorder characterized by delayed opacification of coronary vessels with normal coronary angiogram. It may be due to endothelial dysfunction and diffuse atherosclerosis. Lipoprotein(a) [Lp(a)] is related to cardiovascular events. Plasma Lp(a) levels have not been studied previously in SCF patients. AIM: We investigated plasma Lp(a) and fibrinogen levels, and their relation to coronary flow rate in patients with SCF. MATERIAL AND METHODS: This cross-sectional study included 50 patients with SCF and 30 age- and sex-matched controls who had normal coronary arteries and normal flow. Coronary flow rates of patients and controls were counted with the thrombolysis in myocardial infarction (TIMI) frame count. Plasma Lp(a) and fibrinogen levels were measured in SCF patients and controls, with routine biochemical tests. RESULTS: There were no significant differences between the two groups with respect to plasma Lp(a) (21 mg/dl vs. 14 mg/dl, p = 0.11) and fibrinogen (278 mg/dl vs. 291 mg/dl, p = 0.48) levels. The TIMI frame count was not correlated with plasma Lp(a) (r = 0.13, p = 0.25) or fibrinogen (r = -0.14, p = 0.28) levels. CONCLUSIONS: Our results show that there is no significant association between SCF and Lp(a) and fibrinogen levels.

Plasma concentrations of asymmetric dimethylarginine, nitric oxide and homocysteine in patients with slow coronary flow.

OBJECTIVES: Slow coronary flow (SCF) is slow progression of contrast agent in the coronary arteries in the absence of stenosis in epicardial coronary vessels. Endothelial dysfunction and diffuse atherosclerosis have been proposed for the etiology of SCF. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, levels are associated with an increased risk of endothelial dysfunction and atherosclerosis. ADMA levels may be increased by homocysteine. The aim of this study was to evaluate the relationship between ADMA, nitric oxide and homocysteine in patients with SCF. METHODS: The study group consisted of 50 patients with SCF. An age- and gender-matched control group was composed of 30 patients with normal coronary arteries and normal coronary flow on coronary angiography. We measured ADMA, nitric oxide and homocysteine plasma concentrations in all patients. RESULTS: Plasma nitric oxide concentrations were significantly lower in the SCF group than in the control group (11.4 ± 6, 16.1 ± 9, p = 0.02). Plasma ADMA concentrations (0.9 ± 0.3, 0.7 ± 0.3, p = 0.01) and plasma homocysteine concentrations (12.4 ± 5, 9.8 ± 2, p = 0.03) were significantly higher in the SCF group than control group. The mean TIMI frame count (TFC) was significantly correlated with plasma ADMA (r = 0.26, p = 0.02) and homocysteine (r = 0.28, p = 0.02) concentrations, but not with nitric oxide concentrations (r = - 0.18, p = 0.13). In linear regression analysis, plasma ADMA concentrations (ß = 4.6, p = 0.005) and homocysteine concentrations (ß = 0.2, p = 0.03) were independently and positively associated with mean TFC. CONCLUSION: Our results suggest that plasma concentrations of ADMA and homocysteine are increased in SCF and also that these are independent predictors of SCF.

Protective effects of ß-glucan against oxidative injury induced by 2.45-GHz electromagnetic radiation in the skin tissue of rats.

In recent times, there is widespread use of 2.45-GHz irradiation-emitting devices in industrial, medical, military and domestic application. The aim of the present study was to investigate the effect of 2.45-GHz electromagnetic radiation (EMR) on the oxidant and antioxidant status of skin and to examine the possible protective effects of ß-glucans against the oxidative injury. Thirty-two male Wistar albino rats were randomly divided into four equal groups: control; sham exposed; EMR; and EMR + ß-glucan. A 2.45-GHz EMR emitted device from the experimental exposure was applied to the EMR group and EMR + ß-glucan group for 60 min daily, respectively, for 4 weeks. ß-glucan was administered via gavage at a dose of 50 mg/kg/day before each exposure to radiation in the treatment group. The activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), as well as the concentration of malondialdehyde (MDA) were measured in tissue homogenates of the skin. Exposure to 2.45-GHz EMR caused a significant increase in MDA levels and CAT activity, while the activities of SOD and GSH-Px decreased in skin tissues. Systemic ß-glucan significantly reversed the elevation of MDA levels and the reduction of SOD activities. ß-glucan treatment also slightly enhanced the activity of CAT and prevented the depletion of GSH-Px activity caused by EMR, but not statistically significantly. The present study demonstrated the role of oxidative mechanisms in EMR-induced skin tissue damages and that ß-glucan could ameliorate oxidative skin injury via its antioxidant properties.

The protective effect of adrenomedullin on renal injury, in a model of abdominal aorta cross-clamping.

Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. The aim of this study was to examine the effect of adrenomedullin (AM) on kidney injury induced by infrarenal abdominal aortic IR in rats. Thirty-two Wistar Albino rats were randomized into four groups (eight per group) as follows: Control group, IR group (120-minute ischemia and 120-minute reperfusion), IR + AM group (a bolus intravenously of 0.05 µg/kg/min AM), and control + AM group. At the end of the experiment, blood and kidney tissue specimens were obtained for biochemical analysis. Immunohistological evaluation of the rat kidney tissues was also done. IR significantly increased (p < 0.05 vs control group) and AM significantly decreased (p < 0.05 vs. IR group) all of the biochemical parameters. Immunohistological evaluation showed that AM attenuated morphological changes as apoptosis associated with kidney injury. The results of this study indicate that AM attenuates both biochemically and immunohistopathologically kidney injury induced by aortic IR in rats.

Aspirin increases NMDA receptor subunit 2A concentrations in rat hippocampus.

The N-methyl-d-aspartate receptor (NMDAR), a heteromeric protein, is a glutamate receptor that has three classes of subunits: NR1, NR2, and NR3. It has been reported that these receptors are involved in synaptogenesis, synaptic plasticity, and many other processes in the central nervous system. The aim of this study is to investigate the efficacy of aspirin on hippocampal NMDARs. Sixteen rats were studied in two groups, with eight animals in each group. The first group was the control group, and the second one was the aspirin-given group. Aspirin (acetylsalicylic acid) was administered orally to the rats (200 mg/kg). Tissue samples were obtained after 3 h. The brain was removed, and both hippocampi were dissected out for evaluation. It was found that acute doses of aspirin caused increases on the levels of NMDAR 2A (NR2A) receptors and malondialdehyde (MDA), the end product of lipid peroxidation. Production was significantly increased in the aspirin-given group. We know that MDA is a marker for free radical-mediated tissue damage. In conclusion, lipid peroxidation, caused by acute doses of aspirin may lead to excitotoxicity effects by a hippocampal NR2A-mediated mechanism.

Caffeic acid phenethyl ester modulates gentamicin-induced oxidative nephrotoxicity in kidney of rats.

In this study, the modulator effect of caffeic acid phenethyl ester (CAPE) on the oxidative nephrotoxicity of gentamicin in the kidneys of rats was investigated by determining indices of lipid peroxidation and the activities of antioxidant enzymes as well as by histological analyses. Forty female Wistar albino rats were randomly divided into four groups, namely control, gentamicin, CAPE, and gentamicin plus CAPE. On the 12th day of the study, all rats were sacrificed and then blood samples and kidneys were taken. Lipid peroxidation and nitric oxide levels, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) enzyme activities, and histological evaluation were measured in kidneys of rats. Levels of blood urea nitrogen and creatinine were studied in serum. CAPE with gentamicin caused decreases in lipid peroxidation, nitric oxide, urea nitrogen, and creatinine levels, although it caused increases in CAT, GSH-Px, and SOD activities when compared with gentamicin alone. In addition, on histological evaluation, the renal damage caused by gentamicin alone appeared much higher than that caused by CAPE plus gentamicin. It is concluded that oxidative stress plays a critical role in causing gentamicin nephrotoxicity and that this nephrotoxicity may be significantly reduced by CAPE.

The impact of smoking status on antioxidant enzyme activity and malondialdehyde levels in chronic periodontitis.

BACKGROUND: The aim of this study is to investigate the impact of smoking status on the systemic and local superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities and malondialdehyde (MDA) levels in subjects with chronic periodontitis (CP). METHODS: Sixty-five CP patients (23 smokers [CP-S], 23 former smokers [CP-FS], and 19 non-smokers [CP-NS]) and 20 periodontally healthy non-smoker controls (PH-NS) were included in the study. After the clinical measurements, serum and gingival tissue samples were collected. SOD, GSH-Px, and CAT activities and MDA levels in hemolysates and gingival tissue samples were spectrophotometrically assayed. RESULTS: Blood MDA levels in all the periodontitis groups were higher than in the PH-NS group but only the difference between CP-FS and PH-NS groups was significant (P <0.01). Gingival tissue MDA levels in the periodontitis groups were significantly higher than that in the control group (P <0.01). However, the control group had the highest gingival SOD, GSH-Px, and CAT activities compared with all the periodontitis groups (P <0.01). The CP-S group had the highest gingival MDA levels and SOD, GSH-Px, and CAT activities among the periodontitis groups, whereas the lowest values were observed in the CP-NS group (P <0.01). The blood and gingival MDA levels in the CP-FS group were similar in the CP-NS group, whereas they were lower than in the CP-S group. CONCLUSIONS: Systemic and local MDA levels are increased by smoking in addition to the impact of periodontitis. The decreased local SOD, GSH-Px, and CAT activities observed in periodontitis patients may increase with smoking.

Adrenomedullin attenuates aortic cross-clamping-induced myocardial injury in rats.

BACKGROUND: In this study we investigate the effects of adrenomedullin on myocardial injury after ischemia-reperfusion (I/R) after abdominal aortic surgery. METHODS: Thirty-two Wistar rats were randomized into 4 groups (n = 8) as follows: control group (sham laparotomy), the aortic I/R group, aortic I/R plus adrenomedullin group (underwent aortic I/R periods, and received a bolus intravenous injection of .05 µg/kg/min adrenomedullin), and the control plus adrenomedullin group. RESULTS: Biochemical analysis showed that aortic I/R significantly increased (P < .05) the plasma levels of troponin-I and tumor necrosis factor-α, and the myocardial tissue levels of malondialdehyde, superoxide dismutase, catalase, and angiotensin II, whereas aortic I/R plus adrenomedullin significantly decreased these same factors (P < .05). Aortic I/R significantly increased (P < .05) myocardial tissue levels of nitric oxide whereas aortic I/R plus adrenomedullin significantly increased the same factor (P < .05). CONCLUSIONS: These results indicate that adrenomedullin has protective effects against myocardial injury induced by abdominal aortic I/R in rats.