The Potential Role of RANTES in Post-Stroke Therapy.

One of the key response mechanisms to brain damage, that results in neurological symptoms, is the inflammatory response. It triggers processes that exacerbate neurological damage and create the right environment for the subsequent repair of damaged tissues. RANTES (Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted) chemokine(C-C motif) ligand 5 (CCL5) is one of the chemokines that may have a dual role in stroke progression involving aggravating neuronal damage and playing an important role in angiogenesis and endothelial repair. This study concerned patients with ischemic stroke (AIS), whose CCL5 concentration was measured at various time intervals and was compared with the control group. In addition, the effect of this biomarker on neurological severity and functional prognosis was investigated. Compared to healthy patients, a higher concentration of this chemokine was demonstrated in less than 4.5 h, 24 h and on the seventh day. Differences in CCL5 levels were found to be dependent on the degree of disability and functional status assessed according to neurological scales (modified Rankin Scale, National Institutes of Health Stroke Scale). In addition, differences between various subtypes of stroke were demonstrated, and an increase in CCL5 concentration was proven to be a negative predictor of mortality in patients with AIS. The deleterious effect of CCL5 in the acute phase of stroke and the positive correlation between the tested biomarkers of inflammation were also confirmed.

Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics.

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, is one of the non-enzymatic antioxidants. It not only modulates the perianal rhythm but also has anti-inflammatory properties and protects against stress-induced changes. The focus of this research was to evaluate the concentration of the carbonyl groups and melatonin metabolite in time in patients with acute ischemic stroke that were treated with intravenous thrombolysis. This included a comparison of the functional status of patients assessed according to neurological scales with the control sample comprising healthy people. The studies showed that the serum concentrations of carbonyl groups, which were elevated in patients with ischemic stroke (AIS) in comparison to the control samples, had an impact on the patients' outcome. A urine concentration of the melatonin metabolite, which was lower in patients than controls, was related to functional status after 24 h from cerebral thrombolysis. It shows that determination of carbonyl groups at different time intervals may be an important potential marker of protein damage in patients with AIS treated with cerebral thrombolysis, and that impaired melatonin metabolism induces a low antioxidant protection. Thus, due to the neuroprotective effects of melatonin, attention should also be paid to the design and conduct of clinical trials and hormone supplementation in AIS patients to understand the interactions between exogenous melatonin and its endogenous rhythm, as well as how these relationships may affect patient outcomes.

Selected Mediators of Inflammation in Patients with Acute Ischemic Stroke.

During a stroke, a series of biochemical and metabolic changes occur which eventually lead to the death of cells by necrosis or apoptosis. This is a multi-stage process involving oxidative stress and an inflammatory response from the first signs of occlusion of a blood vessel until the late stages of regeneration and healing of ischemic tissues. The purpose of the research was to assess the concentration of pro-inflammatory cytokines IL-6 and TNF-α in the blood serum of patients with ischemic stroke (AIS) and to investigate their role as new markers in predicting functional prognosis after thrombolytic therapy. The researches have shown that the concentrations of the measured biomarkers were higher compared to the control group. Serum levels of IL-6 and THF-α before the initiation of intravenous thrombolysis were lower in the subgroup of patients with a favourable functional result (mRS: 0−2 pts) compared to the group of patients with an unfavourable functional result (mRS: 3−6 pts). A positive correlation was found between the concentration of IL-6 and TNF-α in patients with AIS during <4.5 h and on one day after the onset of stroke, which means that the concentration of IL-6 increases with the increase in TNF-α concentration. It has also been shown that higher levels of IL-6 in the acute phase of stroke and on the first and seventh days, and TNF-α during onset, were associated with poorer early and late prognosis in patients treated with intravenous thrombolysis. A relationship was found between the level of IL-6 and TNF-α in the subacute AIS and the severity of the neurological deficit. It has been shown that the investigated biomarkers may be a prognostic factor in the treatment of thrombolytic AIS.

Microbial Synthesis of (S)- and (R)-Benzoin in Enantioselective Desymmetrization and Deracemization Catalyzed by Aureobasidium pullulans Included in the Blossom Protect™ Agent.

In this study, we examined the Aureobasidium pullulans strains DSM 14940 and DSM 14941 included in the Blossom Protect™ agent to be used in the bioreduction reaction of a symmetrical dicarbonyl compound. Both chiral 2-hydroxy-1,2-diphenylethanone antipodes were obtained with a high enantiomeric purity. Mild conditions (phosphate buffer [pH 7.0, 7.2], 30 °C) were successfully employed in the synthesis of (S)-benzoin using two different methodologies: benzyl desymmetrization and rac-benzoin deracemization. Bioreduction carried out with higher reagent concentrations, lower pH values and prolonged reaction time, and in the presence of additives, enabled enrichment of the reaction mixture with (R)-benzoin. The described procedure is a potentially useful tool in the synthesis of chiral building blocks with a defined configuration in a simple and economical process with a lower environmental impact, enabling one-pot biotransformation.

Effect of IL-6 and hsCRP Serum Levels on Functional Prognosis in Stroke Patients Undergoing IV-Thrombolysis: Retrospective Analysis.

PURPOSE: We evaluated the relationship between pretreatment IL-6 and hsCRP levels, symptom severity and functional outcome of patients with acute ischemic stroke (AIS) treated with IV-thrombolysis. PATIENTS AND METHODS: IL-6 and hsCRP samples were obtained from 83 consecutively treated Caucasian patients with AIS prior to initiation of IV-thrombolysis. Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS), whereas functional outcome was assessed with modified Rankin Scale (mRS). The commercially available sets of enzymatic immune tests were used to estimate the concentrations of inflammatory markers in serum. RESULTS: Medians of IL-6 serum concentrations prior to IV-thrombolysis were lower in patients with favorable (mRS 0-2 pts) functional outcome than in those with unfavorable (mRS 3-6 pts) functional outcome, both at hospital dismission (5.92: 2.30-7.71 vs 9.46: 3.79-17.29 pg/mL; p<0.01) and on the ninetieth day from stroke onset (5.87: 2.30-10.58 vs 10.9: 5.94-17.28 pg/mL; p<0.01). There were no existing differences regarding hsCRP levels between groups (2.49: 0.11-9.82 vs 4.44: 0.32-9.87 mg/dL; p=0.30 and 2.57: 0.11-2.57 vs 2.83: 0.32-9.32 mg/dL; p=0.75, respectively). Patients with lacunar strokes were characterized by lower median of IL-6 (5.96: 2.87-13.0% vs 7.29: 2.30-17.28; p=<0.02) and hsCRP (2.25: 0.11-9.82 vs 4.84: 0.35-9.87; p=0.01) than those with nonlacunar infarctions. Multivariate analysis showed an impact of IL-6 on mRS measured on hospital dismission and after three months, regardless of their initial NIHSS, presence of hemorrhagic transformation and type 2 diabetes. No impact of hsCRP, lacunar etiology and patients' age on functional outcome existed. CONCLUSION: Regardless of the stroke etiology, pretreatment of IL-6, but not of hsCRP levels, may help to predict functional outcome after IV-thrombolysis independently of symptom severity and stroke complications.

The Role of Selected Pro-Inflammatory Cytokines in Pathogenesis of Ischemic Stroke.

Stroke is currently one of the most common causes of death and disability in the world, and its pathophysiology is a complex process, involving the oxidative stress and inflammatory reaction. Unfortunately, no biochemical factors useful in the diagnostics and treatment of stroke have been clearly established to date. Therefore, researchers are increasingly interested in the inflammatory response triggered by cerebral ischemia and its role in the development of cerebral infarction. This article gives an overview of the available literature data concerning the role of pro-inflammatory cytokines in acute stroke. Detailed analysis of their role in cerebral circulation disturbances can also suggest certain immune response regulatory mechanisms aimed to reduce damage to the nervous tissue in the course of stroke.

Effect of chemical structure of benzofuran derivatives and reaction conditions on enantioselective properties of Aureobasidium pullulans microorganism contained in Boni Protect antifungal agent.

Bioorganic asymmetric reduction of carbonyl compounds is one of the most important fundamental and practical reactions for producing chiral alcohols. The stereoselective bioreduction of prochiral ketones of benzofuran derivatives in the presence of yeast-like fungus Aureobasidium pullulans contained in the antifungal Boni Protect agent was studied. Biotransformations were carried out under moderate conditions in an aqueous and two-phase system and without multiplication of the bioreagent. Despite similar chemical structure, each of the used ketone has been reduced with varying efficiency and selectivity. One of the reasons for these results is the presence of a whole set of oxidoreductases in A. pullulans cells that are sensitive to the smallest changes in the structure of prochiral substrate. The unsymmetrical methyl ketones were biotransformed with the highest selectivity. Aureobasidium pullulans microorganism is less effective in the reduction of unsymmetrical halomethyl ketones. The presence of a heteroatom in the alkyl group significantly decreases the selectivity of the process. Finally, as a result of the preferred hydride ion transfer from the dihydropyridine ring of the cofactor to the carbonyl double bond on the re side, secondary alcohols of the S and R configuration were obtained with moderate to high enantioselectivity (55-99%).

The application of safe for humans and the environment Polyversum antifungal agent containing living cells of Pythium oligandrum for biotransformation of prochiral ketones.

This report presents the whole-cell biotransformation of benzofuranyl-methyl ketone derivatives with the application of Polyversum antifungal agent containing Pythium oligandrum microorganism. Stereochemistry of the reduction of prochiral substrates was modified by the bioconversion conditions (concentration of reagents, a source of the carbon atom, biotransformation medium). In optimized conditions enantioselective process was noted. Secondary alcohols with excellent enantiomeric purity and high yields were obtained. The enantiomeric excess and conversion degree of 1-(benzofuran-2-yl)ethanol, 1-(7-ethylbenzofuran-2-yl)ethanol and 1-(3,7-dimethylbenzofuran-2-yl)ethanol were 99%/98.1%, 94%/94.4% and 99%/72.6%, respectively. In the presence of P. oligandrum, one of the enantiotopic hydrides of the dihydropyridine ring coenzyme is selectively transferred to a re side of the prochiral carbonyl group to give products with S configuration. This study demonstrates an inexpensive, eco-friendly approach in synthesis of optically pure benzofuran derivatives and can be an interesting alternative to organocatalysis. Furthermore, this method can be used in biotechnology processes due to its good chemical performance and a high degree of product isolation.

Lipase-catalyzed enantioselective transesterification of prochiral 1-((1,3-dihydroxypropan-2-yloxy)methyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione in ionic liquids.

The application of ionic liquids as solvents for transesterification of prochiral pirymidine acyclonucleoside using lipase (EC 3.1.1.3) Amano PS from Burkholderia cepacia (BCL) is reported. The effect of using medium reaction, acyl group donor, and temperature on the activity and enantioselectivity of BCL was studied. From the investigated ionic solvents, the hydrophobic ionic liquid [BMIM]PF6 ] was the preferred medium for enzymatic reactions. However, the best result was obtained in the mixture [BMIM][PF6 ]:TBME (1:1 v/v) at 50°C. Enzyme activity and selectivity in [BMIM][PF6 ]:TBME (1:1 v/v) was slightly higher in than in conventional organic solvents (for example, TBME), and in this condition, good activity and enantioselectivity were associated with unique properties of ionic liquid such as hydrophobicity and high polarity. Independently of solvents, monester of (R)-configuration was obtained in excess. Under optimal conditions, desymmetrization of the prochiral compound using different acyl donors was performed. If vinyl butyrate was used as the acylating agent, BCL completely selectively acylated enantiotopic hydroxyl groups.

Biomarkers of antioxidant status and lipid peroxidation in elderly patients with hypertension.

OBJECTIVE: The objective of the present study was to examine selected parameters of the blood redox system in elderly patients with hypertension.examine selected parameters of the blood redox system in elderly patients with hypertension. METHODS: We analyzed differences in redox-associated molecules and enzymes among elderly hypertensive subjects (age above 65 years, n = 49) and two groups of normotensive subjects (<65 years old - Control group I; n = 27, and >65 - Control group II; n = 30). RESULTS: Decreased activity of antioxidant enzymes, increased lipid peroxidation and reduced production of nitric oxide were observed in hypertensive subjects, compared to healthy younger controls, or those of the same age. In healthy controls, an age-related decrease in the production of nitric oxide and the activities of SOD-1 and GPx-1 was also evident. The pathology of hypertension was characterised by further, significant decreases in the values of these parameters. When the subgroups of females and males were compared to their respective controls, a compromised redox balance was observed that was more evident in female hypertensives. DISCUSSION: Hypertension in elderly patients is accompanied by changes in biomarkers of antioxidant status and lipid peroxidation status, which significantly differ from those observed in healthy ageing subjects. Our study also suggests that the relationship of gender and changes in redox balance with regard to hypertension should be further explored.

Pilot study: Raman spectroscopy in differentiating premalignant and malignant oral lesions from normal mucosa and benign lesions in humans.

BACKGROUND: Current practice for differentiating tissue lesions are based on histopathological criteria. This process is subject to error. The purpose of this study was to test whether an alternative, tissue-based molecular signatures Raman spectra could be used to differentiate premalignant and malignant lesions from normal mucosa or benign lesions. METHODS: Eighteen treatment naive subjects with histologically diagnosed oral disease were studied by comparing the Raman spectra of lesions with contralateral healthy sites. Principle component and multivariate analysis were used to predict which of the tissue groups the average spectrum of each lesion or normal tissue belonged. RESULTS: The average spectra were clearly different between premalignant and malignant lesions and those derived from normal, benign tissues. Premalignant and malignant lesions could be predicted with 100% sensitivity and 77% specificity. CONCLUSION: Raman spectroscopy (RS) offers the potential to provide point of care diagnosis of oral disease using a noninvasive, convenient, and relatively inexpensive technology.

Age-related changes in an antioxidant defense system in elderly patients with essential hypertension compared with healthy controls.

BACKGROUND AND AIMS: Oxidative stress has been reported to increase with aging. Oxidative stress is also associated with hypertension, and antioxidant treatment has been shown to enhance antioxidant defense system. We therefore aimed to analyze the relationship between aging and some markers of oxidative stress in elderly patients with essential hypertension compared with healthy controls. MATERIAL AND METHODS: Blood was collected from 18 patients with essential hypertension and 21 age- and sex-matched healthy controls aged over 65. Patients were on their usual medications while participating in the study. Oxidative stress parameters were investigated by measuring the concentration of glutathione (GSH) in whole blood and activities of glutathione peroxidase (GPx-1), glutathione reductase (GR), catalase (CAT), and Cu-Zn superoxide dismutase (CuZn SOD, SOD-1) in erythrocytes. GSH, GPx-1, GR, CAT, and CuZn SOD correlations with age were expressed as Pearson product-moment correlation coefficient r. Independent-samples T test was used to compare mean values of parameters between groups. RESULTS: (1) Among all parameters analyzed herein, the activity of SOD-1 showed the most explicit decrease in relation to age, both in healthy controls and hypertensive subjects with r values of -0.54 (P = 0.05) and -0.68 (P < 0.01), respectively. (2) Age-related changes in parameters of oxidative stress did not differ significantly between groups. (3) Mean activity of SOD-1 was significantly higher (P < 0.05) in elderly hypertensives (2341.7 ± 213.71 U/g Hb) when compared with healthy controls (2199.7 ± 213.66 U/g Hb). (4) Mean GSH level was significantly higher (P < 0.01) in patients (3.1 ± 0.29 mmol/l) than in controls (2.8 ± 0.37 mmol/l). (5) Increased level of GSH in hypertension was followed by significantly (P < 0.01) higher activity of GR in this group when compared with controls (83.4 ± 15.25 and 64.1 ± 9.40 U/g Hb, respectively). CONCLUSIONS: (1) The antioxidant barrier changes in elderly subjects with senescence. (2) CuZn SOD activity is negatively correlated with age and this association is not altered by factors that modulate the enzyme activity, such as hypertension and antihypertensive treatment. (3) Significantly higher concentration of GSH and significantly higher GR activity in patients may suggest a significant role of GSH metabolism in the pathogenesis of hypertension, as well as its contribution to the effect of antihypertensive treatment.

Effects of coenzyme Q10 supplementation on activities of selected antioxidative enzymes and lipid peroxidation in hypertensive patients treated with indapamide. A pilot study.

INTRODUCTION: An increase in oxidative stress is strongly documented in hypertensive patients. In blood vessels, oxidative stress increases the production of superoxide anion (O(2) (•-)) that reacts with nitric oxide (NO) and impairs the ability of endothelium to relax. Many reports indicate a beneficial effect of coenzyme Q10 (CoQ) in hypertension. Coenzyme Q10 therapy may lower O(2) (•-) and thus decrease the complications associated with hypertension. The aim of our study was to evaluate the effects of CoQ supplementation on antioxidative enzyme activities and lipid peroxidation in elderly hypertensive patients. MATERIAL AND METHODS: We determined the activities of superoxide dismutase (SOD-1) and glutathione peroxidase (GSH-Px) and the concentration of malondialdehyde (MDA) in erythrocytes of 27 elderly (mean age 72.5 ±6.1 year) hypertensive patients treated with indapamide at baseline and after 12 weeks of CoQ supplementation (60 mg twice a day) in comparison with 30 healthy elderly volunteers (mean age 76.8 ±8.5 year). RESULTS: Decrease of SOD-1 (p < 0.001) and insignificant reduction of GSH-Px activities and increase of MDA (p < 0.001) level were observed in hypertensive patients in comparison to healthy volunteers before supplementation. Coenzyme Q10 administration resulted in a significant increase only in SOD-1 activity (p < 0.001). CONCLUSIONS: The present study indicates that CoQ improves the most important component of the antioxidant defence system - SOD-1, which is responsible for O(2) (•-) scavenging. Coenzyme Q10 may be used as an additional therapeutic agent for prophylaxis and treatment of hypertension in elderly patients.

Melatonin improves oxidative stress parameters measured in the blood of elderly type 2 diabetic patients.

An elevated oxidative status in the aging organism may be involved in the development of non-insulin dependent diabetes mellitus (NIDDM). Melatonin, a potent antioxidant agent, is essential for glucose homeostasis and regulation. The aim of this study was to determine the influence of melatonin supplementation on the oxidative stress parameters in elderly NIDDM patients. The malondialdehyde (MDA) concentration, Cu-Zn superoxide dismutase (SOD-1) activity in erythrocytes, the level of nitrate/nitrite in plasma and morning melatonin concentration and oxidase activity of ceruloplasmin (Cp) in serum in 15 elderly NIDDM patients at baseline and after the 30 days of melatonin supplementation (5 mg daily) in comparison with levels in 15 healthy elderly volunteers were determined. A significant increase of MDA level and decrease of SOD-1 activity and melatonin concentration were observed in NIDDM patients. Cp oxidase activity and nitrate/nitrite level were similar in both examined groups. Melatonin administration in NIDDM patients resulted in a significant increase in the morning melatonin concentration and SOD-1 activity, and a reduction in the MDA level and Cp oxidase activity. Statistically significant alterations in nitrate/nitrite levels were not observed. These results indicate an improvement of antioxidative defense after melatonin supplementation in the NIDDM individuals and suggest melatonin supplementation as an additional treatment for the control of diabetic complications.

[Time dependent effect of melatonin administration on lipid peroxidation, superoxide dismutase activity and melatonin concentration in the elderly patients with essential arterial hypertension]. / Wplyw melatoniny na procesy peroksydacji lipidów, aktywnosc dysmutazy ponadtlenkowej oraz stezenie melatoniny u osób w podeszlym wieku z pierwotnym nadcisnieniem tetniczym w zaleznosci od czasu suplementacji.

Oxidative stress and melatonin (the pineal hormone) are involved in the pathogenesis of aging and aging-related diseases, including essential arterial hypertension. The aim of study was determination of time dependent effect of melatonin administration on malondialdehyde (MDA) concentration, Cu, Zn-superoxide dismutase (SOD-1) activity and melatonin concentration in the elderly patients with essential arterial hypertension. The study was carried out on 11 patients with essential arterial hypertension (NT group, average 76.7 +/- 10 years), who were treated with thiazide diuretic. The reference group (K) was constituted 13 people without the chronic diseases (average 76.9 +/- 8 years). In the groups NT and K melatonin (Melatonin 5mg, LEKAM) one hour before sleep was administrated. MDA concentration and SOD-1 activity was performed before beginning of experiment and after 15 and after 30 days of the melatonin administration. Melatonin concentration was determined before beginning of experiment and after 30 days of the melatonin administration. Venous blood was taken from the cubital vein at 08.00 am. Melatonin concentration was determined in serum, and MDA content and SOD-1 acitivity were determined in erythrocytes. In NT group in comparison to K group non-significant higher MDA concentration (0.293 +/- 0.03 and 0.286 +/- 0.03 micromol/g Hb, respectively), lower SOD-1 activity (2591 +/- 304.1 and 2630 +/- 301 U/g Hb, respectively) and lower melatonin concentration (7.65 +/- 4.6 and 8.36 +/- 4.7 pg/ml, respectively) were observed. After 15 days of melatonin administration lower MDA concentration and higher SOD-1 activity: in NT group (0.250 +/- 0.03, p < 0.01 and 2757 +/- 299, NS, respectively) and in K group (0.264 +/- 0.03, NS and 3065 +/- 529, p < 0.02, respectively) were measured. After 30 days of supplementation MDA concentration further decreased in NT group (0.247 +/- 0.03, NS) and in K group (0.240 +/- 0.03, p < 0.002). However, after 30 days of melatonin administration in comparison to the results of 15 days the statistically non-significant differences of SOD-1 activity, either in NT group (2680 +/- 332 U/g Hb) and in K group (3012 +/- 417 U/g Hb) were observed. After 30 days of supplementation melatonin concentration increased in NT group (19.57 +/- 11.7 pg/ml, p < 0.01) and in K group (19.33 +/- 17.8 pg/ml, p < 0.05). The results may indicate on the intensification of oxidative stress in elderly patients with essential arterial hypertension and on the beneficial antioxidant effect of melatonin, already after 15 days of supplementation. This results may have indicates on the therapeutic implications.

Antioxidative effects of melatonin administration in elderly primary essential hypertension patients.

The imbalance of the redox state of the aging organism may be involved in the development of primary essential hypertension. Melatonin, a potent antioxidant agent, was found to exert a hypotensive effect and improve the function of the cardiovascular system. The aim of this study was to determine the influence of melatonin supplementation on oxidative stress parameters in elderly primary essential hypertensive (EH) patients, controlled by a diuretic (indapamide) monotherapy. The levels of malondialdehyde (MDA) and reduced glutathione (GSH), activities of Cu-Zn superoxide dismutase (SOD-1), catalase (CAT) and glutathione peroxidase (GSH-Px) in erythrocytes, the plasma level of nitrate/nitrite, the content of carbonyl groups of plasma proteins and morning melatonin levels in the serum of 17 elderly EH patients were determined at the baseline and after the 15th and 30th days of melatonin supplementation (5 mg daily). Melatonin administration resulted in a significant increase in the morning melatonin concentration, SOD-1 and CAT activities, and a reduction in the MDA level. Statistically significant alterations in the levels of GSH, nitrate/nitrite and carbonyl groups and the activity of GSH-Px were not observed. These results indicate an improvement in the antioxidative defense of the organism by melatonin supplementation in the examined group and may suggest melatonin supplementation as an additional treatment supporting hypotensive therapy in elderly EH patients.

Effect of melatonin on the oxidative stress in erythrocytes of healthy young and elderly subjects.

The disturbances in pro- and antioxidant balance may play an important role in the pathomechanism of aging. The pineal hormone melatonin, which exerts effective antioxidative properties, is suggested to be involved in the aging process. The aim of this study was to compare the oxidative stress in erythrocytes of healthy young adults and elderly people, and to determine the influence of melatonin supplementation on measured parameters in both examined groups. The malondialdehyde (MDA) and reduced glutathione levels as well as Cu-Zn superoxide dismutase (SOD-1), catalase, glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and glutathione reductase (GR) activities in erythrocytes and morning serum melatonin concentration in 14 healthy young adults and 14 healthy elderly people at baseline and after the 30th day of melatonin (5 mg daily) supplementation were determined. A significant age effect on increasing the MDA level and decreasing SOD-1, GSH-Px and GR activities as well as melatonin concentration was observed. Melatonin supplementation resulted in a significant increase in melatonin concentration, SOD-1 and GR activities and a decrease in the MDA level in both examined groups. These data indicate an age-related augmentation of oxidative stress in erythrocytes and the improvement of erythrocytic antioxidative defense by melatonin administration. These results might suggest melatonin supplementation to prevent age-related diseases and to prolong the lifespan and improve the quality of life of elderly people.

Effects of perindopril and hydrochlorothiazide on selected indices of oxidative stress in the blood of elderly patients with essential hypertension.

1. The aim of the present study was to determine the effect of hypotensive therapy with a diuretic (hydrochlorothiazide) and an angiotensin-converting enzyme inhibitor (perindopril) on selected oxidative stress parameters in the blood of elderly patients with essential hypertension. 2. Studies were performed in 45 elderly patients with essential hypertension at baseline and after the 45th day of perindopril (n = 25) or hydrochlorothiazide (n = 20) therapy, as well as in 25 young and 25 elderly normotensive subjects. The following parameters were measured: systolic and diastolic blood pressure, nitric oxide (NO), carbonyl groups and malondialdehyde (MDA) concentrations, as well as the activity of ceruloplasmin (Cp) oxidase, Cu-Zn superoxide dismutase (SOD-1) and catalase (CAT). 3. The activity of SOD-1 and NO levels were reduced with age. 4. Compared with elderly controls, hypertensive subjects showed increases in baseline MDA, carbonyl group concentrations and Cp oxidase activity and decreases in NO levels and SOD-1 and CAT activities. 5. Treatment with perindopril, but not hydrochlorothiazide, resulted in significant increases in SOD-1 and CAT activities and decreases in MDA concentration and Cp oxidase activity. Both therapies decreased the level of carbonyl groups and increased NO levels. 6. Angiotensin-converting enzyme inhibitor therapy has significant anti-oxidant effects that may be important in the treatment of elderly patients with essential hypertension.

Production of nitric oxide, lipid peroxidation and oxidase activity of ceruloplasmin in blood of elderly patients with primary hypertension. Effects of perindopril treatment.

BACKGROUND AND AIMS: One of the factors playing a role in both the aging process and the etiopathogenesis of primary hypertension is oxidative stress. The purpose of this work was to estimate the production of nitric oxide (NO), oxidase activity of ceruloplasmin (Cp) and level of malondialdehyde (MDA), the end-product of lipid peroxidation in the blood of elderly patients with primary hypertension. The influence of treatment with the angiotensin-converting enzyme inhibitor perindopril (P) on the above parameters was also ascertained. METHODS: The study was carried out on 37 patients (69-91 yrs) with primary hypertension, treated with perindopril for 6 weeks, and normotensive subjects who constituted the two control groups: 25 (65-96 yrs--K1) and 23 (22-41 yrs--K2). Cp oxidase activity in serum, MDA level expressed as the concentration of substances reacting to thiobarbituric acid in red blood cells, and production of NO (concentration of nitrite/nitrate in plasma) by the Griess reaction were all determined. RESULTS: In the group of patients with hypertension, Cp activity was significantly higher than that in the control groups (K1 and K2). MDA concentrations in the erythrocytes of patients with hypertension were significantly higher than in the control groups and hypertensive patients had a lower NO (nitrite/nitrate) levels in plasma when compared with controls. In patients with hypertension, after only 7 days of therapy a substantial decrease in Cp oxidative activity was found, although the lowest value was observed after 6 weeks of therapy. Nevertheless, significantly lower MDA was observed after 6 weeks of therapy, corresponding to the values obtained in controls (K1 and K2). After 6 weeks of perindopril therapy, NO (nitrite/nitrate) was statistically higher in comparison with the values obtained before therapy. CONCLUSIONS: Results confirm intensification of oxidative stress and disorders in the production of NO in elderly patients with primary hypertension, and indicate the beneficial antioxidant effect of P.

The markers of oxidative stress and activity of the antioxidant system in the blood of elderly patients with essential arterial hypertension.

We estimated the nitrate/nitrite, carbonyl groups, reduced glutathione (GSH) and malondialdehyde (MDA) concentrations and Cu,Zn superoxide dismutase (SOD-1), catalase (CAT), glutathione peroxidase (cGSH-Px) and glutathione S-transferase (GST) activities in the blood of 17 normotensive young subjects (mean age 39+/-7.0 years), 21 normotensive elderly subjects (mean age 82+/-8.2 years) and 38 patients with essential arterial hypertension (mean age 73+/-8.0 years). Our examinations showed that hypertension in the elderly is associated with greater than normal levels of protein and lipid oxidation, decreased nitric oxide concentration and an imbalance in antioxidant status (decreased GSH concentration and SOD-1 activity). The increased activity of GST compensated the decreased activity of cGSH-Px in the blood of hypertensive patients. Our study confirms that the degree of oxidative stress in elderly patients intensifies, especially if said patients have associated essential arterial hypertension.