BACKGROUND: Hypertension is one of the principal risk factors for cardiovascular disease. We aimed to evaluate the impact of hypertension on fibrinolytic balance and endothelial function by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA), tPA/PAI-1 complex and fibrinogen. METHODS: Patients enrolled into the study were divided into four groups: 22 essential hypertensive (EH), 22 white coat hypertensive (WCH), 22 renovascular hypertensive (RH) and 22 normotensive control subjects. Plasma PAI-1, tPA, tPA/PAI-1 complex levels were measured by enzyme linked immunosorbent assays. RESULTS: There was no difference in the systolic and diastolic blood pressure measurements of the EH and RH groups. The four groups were comparable for age, gender, smoking habits and BMI. Patients with EH, RH and WCH had increased plasma levels of PAI-1, tPA, tPA/PAI-1 complex and fibrinogen compared with controls. No fibrinolytic parameter was associated with blood pressure in hypretensive subjects. CONCLUSION: This prospective study showed that fibrinolytic markers such as PAI-1, tPA, tPA/PAI-1 complex are independently associated with the development of hypertension. This supports the hypothesis that disturbances in fibrinolysis precede a cardiovascular event. Therefore, hypertension may be associated with impaired fibrinolysis.

A shift from redox regulation to oxidative damage is known to contribute organ dysfunction and aging-related disorders. Exposure to reactive oxygen species throughout the life-span increases the incidence of several liver diseases. A redox basis of the loss of antioxidant capacity of aged livers has not been fully elucidated in both genders. In the current study, we investigated the gender-dependent relations between protein carbonyl (PCO), a commonly used marker of protein oxidation and other protein oxidation parameters such as advanced oxidation protein products (AOPP) and total thiol (T-SH). Our study also covered other oxidative stress markers, such as malondialdehyde (MDA), lipid hydroperoxides (LHP), and glutathione (GSH) in liver tissue of the male and female aged rats. PCO and AOPP levels in old male and female rats were significantly higher than those in the young control groups (P < 0.001 and P < 0.01, respectively for male rats; P < 0.001 for both parameters in female rats). On the other hand, T-SH levels were not found to be different between young and old rat groups. Plasma MDA levels of old male and female rats were significantly higher compared to those of the young control groups (P < 0.01 and P < 0.001, respectively). LHP levels were only found out to be significantly higher in old female rats when compared to those in young male rats. GSH levels in old male and female rats were significantly lower than in the corresponding young control groups (P < 0.01 for male rats; P < 0.05 for female rats). Our results demonstrated greater susceptibility to hepatic oxidative damage in females than in males. This appears to contradict the general assumption that females are less susceptible to oxidative injury than males are.

Hypercholesterolemia and/or hypertension impair endothelial function in peripheral vasculature; however, their impact on endothelial cells of brain microvessels is unclear. We investigated the effects of hypercholesterolemia on the integrity of the blood-brain barrier (BBB) and the activity of astrocytes during N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension followed by angiotensin (ANG) II. We found significant decreases in superoxide dismutase levels with all treatments except ANG II and L-NAME plus ANG II, and in catalase concentrations except ANG II and cholesterol plus L-NAME. Nitric oxide (NO) concentrations were significantly decreased by L-NAME but significantly increased by cholesterol. L-NAME-stimulated plasma malondialdehyde (MDA), Ox-LDL, and cholesterol levels were significantly augmented by cholesterol. Glutathione (GSH) levels significantly decreased, while MDA, TNF-alpha, and Ox-LDL levels significantly increased in cholesterol and/or L-NAME. The increase in BBB permeability by acute hypertension in hypercholesterolemic hypertensive animals was less than that observed in chronically hypertensive animals. Brain vessels of L-NAME-treated animals showed a considerable loss of immunoreactivity for tight junction proteins, occludin, and ZO-1. Immunoreactivity for occludin and ZO-1 increased in cholesterol plus L-NAME and decreased in cholesterol. Glial fibrillary acidic protein (GFAP) immunoreactivity was seen in few astrocytes in the brain sections of L-NAME-treated animals, but increased in cholesterol plus L-NAME. Positive immunoreactivity for vascular endothelial growth factor (VEGF) was observed in cholesterol and cholesterol plus L-NAME plus ANG II. We suggest that hypercholesterolemia may affect BBB integrity through increasing the expression of tight junction proteins and GFAP and leading to the production of VEGF, at least partly, via increased NO, TNF-alpha, and catalase in hypertensive conditions.

Introduction. The effect of aging on plasma-protein, lipid and DNA oxidation is well documented. However, none of the studies specify the effect of gender. The purpose of this study is to clarify the ambiguity raised in preliminary reports as to gender dependency of oxidative damage in plasma. Methods. In the current study, we investigated the relation between 8-hydroxy-2'-deoxyguanosine levels (8-OHdG), which is a measure of DNA oxidation and protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH), and advanced oxidation protein products (AOPP). Our study also covered other oxidative stress parameters, such as lipid hydroperoxides (LHP), malondialdehyde (MDA), erythrocyte glutathione (GSH), superoxide dismutase (Cu-Zn SOD) and the catalase (CAT) activity in plasma of the male and female aged rats. Results. 8-OHdG and MDA levels in male rats were significantly higher than those in the female group (p < 0.01 for both parameters). T-SH levels were found to be higher in female rats than in the male (p < 0.05). Plasma Cu-Zn SOD activities of male rats were significantly higher compared with those of the female rats (p < 0.05). On the other hand, PCO, AOPP, LHP, GSH levels, and CAT activity were not found to be different between genders. Conclusions. We suggest that increased T-SH levels found in female rats may point to an adaptive reaction to oxidative damage, reflecting 8-OHdG and MDA overproduction. We are of the conviction that the increased 8-OHdG and MDA that we have determined in aged male rats may be a risk factor in the extent of oxidation in plasma.

PURPOSE: To investigate diagnostic values of pleural fluid matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1) and TIMP-2 measurements in tuberculous pleurisy(TP) and malignat pleurisy (MP). METHODS: The study included 24 patients with TP, 22 patients with MP and 15 patients with pleural effusion of non-tuberculous and non-malignant origin as controls. MMP-2,-9 and TIMP-1,-2 levels in pleural fluid were measured by ELISA method. RESULTS: Pleural fluid MMP-2 and MMP-9 levels were higher (P < 0.001, P < 0.001, respectively) in TP than in MP and controls. MP patients have higher pleural fluid MMP-2 and MMP-9 levels (P < 0.01, P < 0.05, respectively) than controls. Pleural fluid TIMP-2 levels were higher (P < 0.01 and P < 0.001, respectively) in MP than in TP and controls. Pleural fluid MMP-9 levels were negatively correlated with pleural fluid TIMP-2 levels (r: 0.464, P=0.029) in patients with MP. CONCLUSIONS: Determination of TIMP-2 in pleural fluid may contribute to differentiate TP from MP. These results suggest that overproduction of MMP-9 and TIMP-2 is associated with accumulation of the pleural effusion in malignancy. Further studies with a greater number of patients are needed to confirm this hypothesis.

BACKGROUND: The aim of this study was to describe current patterns of monitoring and treatment of mad honey intoxication to make recommendations for a more standardized approach to care of patients with mad honey poisoning. METHODS: Patients presenting to emergency departments because of honey poisoning between January and October 2007. Age, length of stay in the emergency department, pulse rate, and systolic and diastolic blood pressure are cited as mean +/- SD. RESULTS: Forty-seven cases presenting to the 3 health institutions during 2007 were investigated. It was determined that patients had ingested "mad" honey between 0.5 and 9 hours (mean +/- SD, 2.8 +/- 1.8 hours) before presentation. Patients' pulse rates were 30 to 77/min (mean +/- SD, 46.6 +/- 12.1/min), and systolic blood pressure ranged from 50 to 140 mm Hg (mean +/- SD, 46.6 +/- 12.1 mm Hg). Patient rhythms on arrival were determined as 37 (7.7%) sinus bradycardia, 6 (12.8%) nodal rhythm, 3 (6.4%) normal sinus rhythm, and 1 (2.1%) complete atrioventricular block. Lengths of stay in hospital were 3.6 +/- 2.2 hours in the first university hospital, 22.2 +/- 3.8 hours in the second university hospital, and 3.4 +/- 1.7 hours in the state hospital. A 0.5 to 2 mg of atropine was given to all patients. CONCLUSIONS: Our study did not reveal any difference in complications or mortality between patients cared for with brief emergency department observation when compared with patients cared for with 1 day inpatient observation.

Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.

ABSTRACT AIM: The present study aimed to investigate the effect of different doses of vitamin C on the oxidative liver injury due to isoniazid in rats METHODS: Rats were divided into four subgroups, each containing 10 rats. Group 1:Control, group 2:INH(50mg/kg/day), group 3:INH(50mg/kg/day)+low-dose vitamin C(100mg/kg/day), group 4:INH(50mg/kg/day)+high-dose vitamin C(1000mg/kg/day). INH and vitamin C were given into their stomachs through an oral tube. After 21 days; measurments were made in both serum and homogenized liver tissues. The levels of glutathione (GSH), superoxide dismutase(SOD) and other biochemical variables were studied by different biochemical methods. Malondialdehyde(MDA), glutathione peroxidase(GSH-px) and vitamin C were studied by commercial kits. RESULTS: AST and ALT values in Group 2 were higher than those in Groups 1, 3 and 4(P < 0.008 for both). Serum and tissue levels of MDA in Group 2 were higher than that in Groups1 and 3 (P < 0.008 for both). There was no difference for the SOD levels between four groups(p = 0.095). Erythrocyte and tissue GSH in Group 2 were higher than that in Groups 1 and 3(P < 0.008 for both). Interestingly, erythrocyte and tissue GSH in Group 4 were lower than those in Group 1(P < 0.008 for both). Erythrocyte level of GSH-px in Group 2 was higher than that in Groups1 and 3(P < 0.008 for both). CONCLUSIONS: Isoniazid induced liver injury is associated with oxidative stress, and co-administiration of low dose vitamin C may attenuate this damage effectively in rat model. The antioxidant effect of high dose vitamin C does not seem more potent compared to low dose.

OBJECTIVE: Our aim was to clarify the effects of hypercholesterolemic diet and administeration of atorvastatin on lipid peroxidation, protein oxidation and oxidative DNA damage in male New Zealand white rabbits. METHODS: We determined malondialdehyde (MDA), protein carbonyl (PCO) and total thiol (T-SH) levels in plasma and liver tissue, glutathione (GSH) levels in erythrocyte and liver tissue, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in plasma. Twenty rabbits were randomly divided into two groups and fed with a high-cholesterol diet (fortified with 1% cholesterol) for 4 weeks. Such rabbits were subjected to either (Group 1) a high-cholesterol diet non-supplemented with atorvastatin (n=10) or (Group 2) a high-cholesterol diet supplemented with atorvastatin (0.3mg atorvastatin per day/kg body weight) for 4 weeks (n=10). A control group (n=5)(Group 3) was fed a cholesterol free diet for 4 weeks. Colorimetric methods were used to determine the level of the oxidative stress markers, except 8-OHdG, which was measured by ELISA. RESULTS: Rabbits were fed with the high-cholesterol diet alone (Group 1) showed higher levels of lipid profile and oxidative protein and DNA damage than compared with dose of the control group (Group 3). Atorvastatin therapy has substantially beneficial effects on oxidative protein and DNA damage in hypercholesterolemic rabbits. CONCLUSIONS: The current findings will, we hope, lead to a new insight into the pathogenesis of atherosclerosis. On the other hand inhibition of protein oxidation and DNA oxidation in the plasma by atorvastatin may be one of the pleiotropic effects of statins, and thus the underlying mechanism needs to be further clarifications.