Sepsis is a life threatening condition that arises when the body's response to an infection injures its own tissues and organs. Sepsis can lead to shock, multiple organ failure and death especially if not recognized early and treated promptly. Molecular mechanisms underlying the systemic inflammatory response syndrome associated with sepsis are still not completely defined and most therapies developed to target the acute inflammatory component of the disease are insufficient. In this s tudy we investigated a possibility of combating sepsis in a mouse model by intravenous treatment with recombinant human tissue non - specific alkaline phosphatase (rhTNAP) derived from transgenic rabbit milk. We induced sepsis in mice by intraperitoneal inje ction of LPS and three hours later treated experimental group of mice by intravenous injection with rhTNAP derived from transgenic rabbits. Such treatment was proved to be physiologically effective in this model, as administration of recombinant rhTNAP suc cessfully combated the decrease in body temperature and resulted in increased survival of mice (80 % vs. 30 % in a control group). In a control experiment, also the administration of bovine intestinal alkaline phosphatase by intravenous injection proved to be effective in increasing survival of mice treated with LPS. Altogether, present work demonstrates the redeeming effect of the recombinant tissue non -specific AP derived from milk of genetically modified rabbits in combating sepsis induced by LPS., B. Bender, M. Baranyi, A. Kerekes, L. Bodrogi, R. Brands, P. Uhrin, Z. Bösze., and Obsahuje bibliografii
The effect of antigenic bacterial lysate IRS-19 on the recovery of blood cells was studied in mice injured by a single dose of 7 Gy irradiation. The preirradiation administration of IRS-19 accelerated the recovery of leukocytes, reticulocytes and platelets in peripheral blood. The recovery of leukocytes 9-14 days after irradiation in protected animals was accompanied by a higher level of band forms of granulocytes as well as activated lymphoid and monocytoid cells., N.O. Macková, P. Fedoročko., and Obsahuje bibliografii
Red palm oil (RPO) is a rich natural source of antioxidant vitamins, namely carotenes, tocopherols and tocotrienols. However, it contains approximately 50 % saturated fatty acids the regular consumption of which could negatively modify lipid profile. The aim of our study was to test whether 7 weeks of RPO supplementation (1 g/kg body weight/day) would affect blood glucose and lipid metabolism in adult male Wistar rats with altered thyroid status. We induced hypothyroidism and hyperthyroidism in rats by oral administration of either methimazole or mixture of thyroid hormones. Different thyroid status (EU - euthyroid, HY - hypothyroid and HT - hyperthyroid) was characterized by different serum thyroid hormones levels (total and free thyroxine and triiodothyronine), changes in the activity of a marker enzyme of thyroid status - liver mitochondrial glycerol-3-phosphate dehydrogenase, and altered absolute and relative heart weights. Fasting blood glucose levels were higher in HT rats in comparison with EU and HY rats, but the changes caused by RPO supplementation were not significant. The achievement of the HY status significantly increased serum levels of total cholesterol, as well as with high-density lipoproteincholesterol and low-density lipoprotein-cholesterol: 2.43±0.15, 1.48±0.09, 0.89±0.08 mmol/l, compared to EU: 1.14±0.06, 0.77±0.06, 0.34±0.05 mmol/l and HT: 1.01±0.06, 0.69±0.04, 0.20±0.03 mmol/l, respectively. RPO supplementation did not increase significantly levels of blood lipids but tended to increase glutathione levels in the liver. In conclusion, RPO supplementation did not induce the presumed deterioration of glucose and lipid metabolism in rats with three well-characterized alterations in thyroid status., H. Rauchová, M. Vokurková, S. Pavelka, I. Vaněčková, N. Tribulová, T. Soukup., and Seznam literatury
Increased amount of collagen type I and decreased amount of type III is described in various pathological processes in the vascular wall. Polyphenols were shown to have protective effect on endothelium, decrease blood pressure and prevent oxidative damage induced by various stimuli. Tetrachlormethane (CCl4) is a toxic substance with known negative systemic effects induced by free radicals. Chronic administration of CCl4 for 12 weeks led to an increase of collagen type I and a decrease of type III in the wall of aorta. Parallel administration of red wine polyphenols significantly reduced the increase of collagen type I, at the same time the content of type III rose to the level above controls. After 4 weeks of spontaneous recovery no changes were observed. If polyphenols were administered during the recovery period, there was a decrease of type I and an increase of type III collagen content in the aorta. It can be concluded that polyphenols have a tendency to lower the amount of type I and to increase the proportion of type III collagen in the wall of the aorta. These changes are significant in prevention or in regression of changes induced by chronic oxidative stress. This effect of polyphenols is most likely the result of their influence on MMP-1 and TIMP activities through which they positively influence the collagen types I and III content ratio in the vascular wall in favor of the type III collagen., L. Hlavačková ... [et al.]., and Obsahuje seznam literatury
The aim of the present study was to investigate the mechanism of vasorelaxant responses induced by red wine polyphenolic compounds (Provinol). Rings of rat femoral artery with or without functional endothelium were set up in a myograph for isometric recording and precontracted with phenylephrine (10-5 M). Provinol in cumulative doses (10-9 to 10-3 mg/ml) elicited endothelium- and dose-dependent relaxation of the artery with maximal relaxation of 56 % at the concentration of 10-5 mg/ml. The relaxant responses to Provinol correlated well with the increase of NO synthase activity in the vascular tissue after administration of cumulative doses of Provinol (10-9 to 10-3 mg/ml). NG-nitro-L-arginine methylester (L-NAME, 3x10-4 M) significantly attenuated the endothelium-dependent relaxation produced by Provinol. Administration of L-arginine (3x10-5 M) restored the relaxation inhibited by L-NAME. The relaxant responses of Provinol were abolished in the presence of Ca2+-entry blocker, verapamil (10-6 M). Administration of hydrogen peroxide (H2O2) abolished acetylcholine (10-5 M)-induced relaxation of the rat femoral artery, while administration of Provinol (10-5 mg/ml) together with H2O2 helped to maintain the acetylcholine-induced relaxation. Provinol only partially affected the concentration-response curve for the NO donor sodium nitroprusside-induced relaxation in rings without endothelium. In conclusion, Provinol elicited endothelium-dependent relaxation of rat femoral artery by the Ca2+-induced increase of NO synthase activity and by protecting NO from degradation., W. Zenebe, O. Pecháňová, R. Andriantsitohaina., and Obsahuje bibliografii
Flavonoids, polyphenol derivatives of plant origin, possess a broad range of pharmacological properties. A number of studies have found both pro/anti-apoptotic effects for many of these compounds. For these reasons we investigated whether ProvinolsTM, flavonoids obtained from red wine, have anti-apoptotic properties. The investigations have been carried out in rats treated with Cyclosporine A (CsA). In particular, four groups of rats have been treated for 21 days with either olive oil (control group), with CsA, with ProvinolsTM, or with CsA and ProvinolsTM simultaneously. Oxidative stress, systolic blood pressure, body weight, biochemical parameters and different markers of pro/anti-apoptotic pathway were measured. CsA produced an increase of systolic blood pressure, a decrease in body weight, serum creatinine levels, urinary total protein concentration and creatinine clearance. Moreover, CsA induced renal alterations and the translocation of Bax and cytochrome c from cytoplasm to mitochondria and vice versa. These changes activated the caspase cascade pathway, that leads to morphological and biochemical features of apoptosis. ProvinolsTM restored morphological and biochemical alterations and prevented nephrotoxicity. In conclusion, this study may augment our current understanding of the controversial pro-/anti-apoptotic properties of flavonoids and their molecular mechanisms., R. Rezzani ... [et al.]., and Obsahuje seznam literatury
Elevated levels of glucocorticoids lead to the development of obesity and metabolic syndrome. Local glucocorticoid levels are regulated through the enzyme 11 β -hydroxysteroid dehydrogenase 1 (11 β -HSD 1), an enzyme that regenerates active cortisol from inert cortis one. Increased expression of 11 β - HSD 1 in adipose tissue promotes higher body mass index (BMI), insulin resistance, hypertension, and dyslipidemia. Human 11 β - HSD 1 is also responsible for inter-conversion of 7-hydroxylate metabolites of dehydroepiandrosterone (7-OH-DHEA) to their 7-oxo-form. To better understanding the mechanism of the action, we focused on 7-OH- and 7-ox o-DHEA, and their circulating levels during the reductive treatment in adolescent obese patients. We determined plasma levels of 7 α -OH-DHEA, 7 β -OH- DHEA, and 7-oxo-DHEA in 55 adolescent patients aged 13.04- 15.67 years, BMI greater than 90 th percentile. Samples were collected before and after one month of reductive therapy. Circulating levels of 7 α -OH-DHEA decreased during the reductive therapy from 1.727 (1.614; 1.854 , transformed mean with 95 % confidence interval) to 1.530 nm ol/l (1.435; 1.637, p<0.05) in girls and from 1.704 (1.583; 1. 842) to 1.540 nmol/l (1.435; 1.659, p<0.05) in boys. With regard to the level of 7-oxo-DHEA, a significant reduction from 1. 132 (1.044; 1.231) to 0.918 nmol/l (0.844; 1.000, p<0.05) was found after the treatment, but only in boys. No significant difference in 7 β -OH-DHEA levels was observed. In conclusions, diminished levels of 7 α -OH-DHEA indicate its possible effect on activity of 11 β -HSD 1. Further studies are necessary to clarify whether competitive substrates for 11 β -HSD 1 such as 7 α -OH-DHEA could inhibit production of glucocorticoids and may be involved in metabolic processes leading to reduction of obesity., L. Máčová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Steroids are important components in the pathophysiology of Alzheimer’s disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5α-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD., M. Vaňková, M. hill, M. Velíková, J. Včelák, G. Vacínová, P. Lukášová, D. Vejražková, K. Dvořáková, R. Rusina, I. Holmerová, E. Jarolímová, H. Vaňková, B. Bendlová., and Obsahuje bibliografii
We examined the involvement of phosphatidylinositol 3-kinase (PI3K) and its effector protein ki nase B (Akt) in cardioprotective effects of ischemic preconditioning (PC) with particular regards to its role in the protection against ischemia-induced arrhythmias in isolated perfused rat heart. PI3K/Akt inhibitor wortmannin (100 nM) was administered 15 min prior to 30-min regional (left anterior descending coronary artery occlusion) ischemia for the study of ischemic arrhythmias in the hearts perfused at constant coronary flow or prior to 30-min global ischemia followed by 2-h reperfusion for the infarct size (IS) determination (tetrazolium staining) in the hearts perfused at constant pressure. PC procedure (one cycle of isch emia/reperfusion, 5 min each) significantly reduced the total number of ventricular premature complexes (PVC) and severity of arrhythmias (arrhythmia score; AS) over the whole period of left anterior descending coronary artery occlusion in comparison with non-PC controls (PVC 166±40; AS 1.6±0.2 vs . 550±60 and 3.2±0.2; respectively; P<0.05). In a setting of global ischemia/reperfusion, PC decreased IS (in % of the left ventricle, LV) by 73 %. Pretreatment with wortmannin modified neither arrhythmogenesis nor IS in the non-PC hearts. Bracketing of PC with wortmannin did not abolish antiarrhythmic protection (PVC 92±25; AS 1.7±0.2; P<0.05 vs . non-PC hearts). On the other hand, wortmannin increased IS/LV in the PC hearts to 24±1.2 % as compared with 9 ± 0.6 % in the untreated ones (P<0.05). In conclusion, PI3K/Akt inhibition did not affect reduced arrhythmogenesis during ischemia in the PC hearts indicating that in contrast to its positive role in the irreversible myocardial injury, PI3K/Akt activity is not required for protection induced by PC against ischemic arrhythmias in the rat heart., T. Ravingerová, J. Matejíková, D. Pancza, F. Kolář., and Obsahuje bibliografii
Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca2+, respectively. Blood glucose in STZ rats was 4-fold higher (469.64±22.23 mg/dl, n=14) than in Controls (104.06±3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76±2.91 %, n=20) and Control (83.72±2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12±2.28 %, n=20) and Control (76.69±1.92 %, n=30) myocytes. The amplitude of intracellular Ca2+ was also reduced by PHLOR in STZ (82.37±3.16 %, n=16) and Control (73.94±5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62±5.83 %, n=18) and Control (78.32±3.54 %, n=41) myocytes. Myofilament sensitivity to Ca2+ was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca2+ in STZ or Control myocytes. Altered mechanisms of Ca2+ transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats., N. N. Hamouda, M. A. Qureshi, J. M. Alkaabi, M. Oz, F. C. Howarth., and Obsahuje bibliografii