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

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

Enantioselective Bioreduction of Prochiral Pyrimidine Base Derivatives by Boni Protect Fungicide Containing Live Cells of Aureobasidium pullulans

The enzymatic enantioselective bioreduction of prochiral 1-substituted-5-methyl-3-(2-oxo-2-phenylethyl)pyrimidine-2,4(1H,3H)-diones to corresponding chiral alcohols by Boni Protect fungicide containing live cells of Aureobasidium pullulans was studied. The microbe-catalyzed reduction of bulky-bulky ketones provides enantiomerically pure products (96–99% ee). In the presence of A. pullulans (Aureobasidium pullulans), one of the enantiotopic hydrides of the dihydropyridine ring coenzyme is selectively transferred to the si sides of the prochiral carbonyl group to give secondary alcohols with R configuration. The reactions were performed under various conditions in order to optimize the procedure with respect to time, solvent, and temperature. The present methodology demonstrates an alternative green way for the synthesis of chiral alcohols in a simple, economical, and eco-friendly biotransformation

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

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

Effect of melatonin on the chosen markers of oxidative stress in the elderly patients with essential arterial hypertension (a preliminary study)

Wstęp. Stres oksydacyjny oraz hormon szyszynki - melatonina - są związane z patogenezą starzenia się i chorób związanych z wiekiem podeszłym. Celem badań było oznaczenie wpływu suplementacji melatoniną na stężenie dialdedydu malonowego (MDA) i melatoniny oraz aktywności wewnątrzkomórkowej Cu, Zn-dysmutazy ponadtlenkowej (SOD-1) we krwi osób w podeszłym wieku z pierwotnym nadciśnieniem tętniczym. Materiał i metody. W badaniach udział wzięło 10 pacjentów z pierwotnym nadciśnieniem tętniczym, leczonych diuretykiem (śr. 80,2 &#177; 10 lat) oraz 8 osób z prawidłowym ciśnieniem bez chorób o poznanej etiologii wolnorodnikowej, które stanowiły grupę odniesienia (średnia wieku 79,4 &#177; 6 lat). Badani przez 30 dni na godzinę przed snem przyjmowali 5 mg melatoniny (firmy LE-KAM). Materiał do badań stanowiła krew pobierana o godzinie 8.00 przed rozpoczęciem eksperymentu i po 30 dniach suplementacji. W surowicy oznaczano stężenie melatoniny, a w hemolizacie stężenie MDA oraz aktywność SOD-1.Wyniki. U osób z nadciśnieniem tętniczym stwierdzono niższe stężenie melatoniny (odpowiednio 6,06 &#177; 4,9 i 7,07 &#177; 3,6 pg/ml) oraz wyższe stężenie MDA (0,293 &#177; 0,03 i 0,275 &#177; 0,04 &#181;mol/gHb) i niższą aktywność SOD-1 (2557,1 &#177; 300 i 2745,5 &#177; 279 U/gHb) niż w grupie pacjentów z prawidłowym ciśnieniem. Nie były to jednak różnice znamienne statystycznie. Po suplementacji w grupie zarówno z nadciśnieniem tętniczym, jak i odniesienia stwierdzono znamienny statystycznie spadek stężenia MDA (odpowiednio 0,219 &#177; 0,05 &#181;mol/gHb, p < 0,001 i 0,225 &#177; 0,04 &#181;mol/gHb, p < 0,02) oraz wzrost aktywności SOD-1 (2974,8 &#177; 532 U/gHb, p < 0,01 i 3227,1 &#177; 37 U/gHb, p < 0,01), a także wzrost stężenia melatoniny (15,8 &#177; 11,1 i 14,37 &#177; 12,41 pg/ml), znamienny statystycznie w grupie z nadciśnieniem tętniczym (p < 0,02). Wnioski. Wyniki badań potwierdzają antyoksydacyjne właściwości melatoniny. Suplementację tym hormonem można wykorzystać jako terapię wspomagającą leczenie hipotensyjne u osób w podeszłym wieku.Background. Oxidative stress and the pineal hormone - melatonin - are involved in the pathogenesis of aging and aging-related diseases. The aim of our study was determination of the effect of melatonin administration on malonyldialdehyde (MDA) and melatonin concentrations and the cellular Cu, Zn-superoxide dismutase (SOD-1) activity in the elderly patients with essential arterial hypertension. Material and methods. The study was carried out on 10 patients with essential arterial hypertension, who were cured with thiazide diuretic (average 80.2 &#177; 10 years) and on 8 normotensive patients, who consituted the reference group (average 79.4 &#177; 6 years). They were given 5 mg melatonin (LE&#8211;KAM) in one hour before sleep for 30 days. The material of study was blood, taken at 08.00 am before the beginning of experiment and after 30 days of the melatonin administration. The melatonin concentration was determined in serum, and MDA content and SOD-1 activity were determined in erythrocytes. Results. Lower melatonin concentration (6.06 &#177; 4.9 and 7.07 &#177; 3.6 pg/ml, respectively) and higher MDA content (0.293 &#177; 0.03 and 0.275 &#177; 0.04 &#181;mol/gHb, respectively) and lower SOD-1 activity (2557.1 &#177; 300 and 2745.5 &#177; 279 U/gHb, respectively) were observed in patients with hypertension in comparison to the reference group. These differences were statistically non-significant. After supplementation in the patients with hypertension and in reference group statistically lower MDA concentration (0.219 &#177; 0.05 &#181;mol/gHb, p < 0.001 and 0.225 &#177; 0.04 &#181;mol/gHb, p < 0.02) and higher SOD-1 activity (2974.8 &#177; 532 U/gHb, p < 0.01 and 3227.1 &#177; 37 U/gHb, p < 0.01) were indicated. In examined groups higher melatonin content (15.8 &#177; 11.1 i 14.37 &#177; 12.41 pg/ml) after administration was noted, but these changes were significant only in the patients with hypertension (p < 0.02). Conclusions. The antioxidative properties of melatonin were confirmed in the study. The supplementation of this hormone may be used as supportive therapy in the hypertensive treatment of the elderly people

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