There is increasing evidence that dietary saturated fatty acids (SAFA) have not only an indirect atherogenic effect due to increasing LDL-cholesterol concentration but also a direct effect by activating the inflammation process. This review summarizes several recent publications in this field. The effect of SAFA on the inflammation process mediated by Toll-like receptor 4/NF-κB pathway has been well documented in various in vitro culture studies of macrophages and adipocytes or in their co-culture. In contrast to these in vitro data, in vivo epidemiological studies or clinical experiments in men are less consistent. Well controlled cross-over studies in volunteers might enlighten the differences between saturated and unsaturated fatty acids dietary intake and proatherogenic inflammation effects., R. Poledne., and Obsahuje seznam literatury
The purpose of the present study was to examine the role of the T-786C endothelial nitric oxide synthase (eNOS) gene polymorphism on changes in renal hemodynamics and blood pressure due to Na+ loading. Twenty-eight older (63±1 years), moderately obese (39±2 % fat) hypertensives had th eir glomerular filtration rate (GFR), renal plasma flow (RPF), blood pressure (BP) and plasma nitric oxide (NOx) levels determined after eight days of low (20 mEq) and high (200 mEq) Na+ diets. The two Na+ diets were separated by a 1-week washout period. Subjects were genotyped for the eNOS-786 site and were grouped on whether they were homozygous or heterozygous for the C allele (TC+CC, n=13) or only homozygous for the T allele (TT, n=15). The TC+CC genotype group had a significantly greater increase in diastolic (P=0.021) and mean arterial (P=0.018) BP and a significant decline in both RPF (P=0.007) and GFR (P=0.029) compared to the TT genotype group with Na+ loading. Furthermore, Na+ loading resulted in a significant (P=0.036) increase in plasma NOx in the TT, but not in the TC+CC genotype group as well as a trend (P=0.051) for an increase in urine NOx in TC+CC, but not in the TT genotype group. The increase in BP during Na+ loading in older hypertensives was associated with the eNOS genotype and may be related to changes in renal hemodynamics due to changes in NO metabolism., D. R. Dengel, M. D. Brown, R. E. Ferrell, T. H. Reynolds, M. A. Supiano., and Obsahuje bibliografii a bibliografické odkazy
Natural glucocorticoid hydrocortisone was suggested as a potent substitution for dexamethasone in the treatment of bronchopulmonary dysplasia in neonates. The aim of this study was to investigate whether hydrocortisone is able to affect the expression of apoptotic genes and the intensity of naturally occurring cell death in the developing rat hippocampus. Hormone treatment decreased procaspase-3 and active caspase-3 levels as well as DNA fragmentation intensity in the hippocampal formation of one-week-old rats in 6 h after injection. These changes were accompanied by an upregulation of antiapoptotic protein Bcl-XL, while expression of proapoptotic protein Bax remained unchanged. The action of hydrocortisone was glucocorticoid receptor-independent, as the selective glucocorticoid receptor agonist dexamethasone did not affect either apoptotic protein levels or DNA fragmentation intensity in the hippocampal region. The data are the first evidences for in vivo antiapoptotic effects of hydrocortisone in the developing hippocampus., P. N. Menshanov, ... [et al.]., and Obsahuje seznam literatury
Cadmium (Cd), an environmental and industrial pollutant, poses a potential threat and affects many systems in human and animals. Although several reports on Cd toxicity were presented, the acute effect of Cd on systemic and thrombotic events was not reported so far. Cd (2.284 mg/kg) or saline (control) was injected intraperitoneally (ip), and the systemic parameters were assessed in mice. Compared to control group, acute intraperitoneal injection of Cd, in mice showed significant quickening of platelet aggregation (P<0.001) leading to pial cerebral thrombosis. Likewise, Cd exposure caused a significant increase in white blood cell numbers (P<0.05) indicating the occurrence of systemic inflammation. Also, alanine aminotransferase (ALT) (P<0.05) and creatinine (P<0.01) levels were both significantly increased. Interestingly, the superoxide dismutase activity was significantly decreased in Cd treated group compared to control group (P<0.001), suggesting the occurrence of oxidative stress. We conclude that the Cd exposure in mice causes acute thromboembolic events, oxidative stress and alter liver and kidney functions., M.A. Fahim ... [et al.]., and Obsahuje seznam literatury
We investigated the effects of telmisartan, the blocker of angiotensin II receptor 1, on the regulation of systolic blood pressure (SBP) and oxidative stress through endothelial nitric oxide (NO) release in spontaneously hypertensive rats (SHRs). SHRs randomly received placebo, oral feeding of telmisartan (5 mg/kg or 10 mg/kg) every day and Wistar-Kyoto rats (WKYs) served as normotensive control. The SBP of rat was measured before and weekly thereafter. After a total of 8-week treatment, rats were killed for experimental measurements. Parameters that subject to measurements in isolated aorta endothelial cells include: NO concentration, protein expression levels of angiotensin II receptor 1, nitrotyrosine, 8-isoprostane, SOD, PI3K, Akt, AMPK and eNOS. In addition, L-NMMA, a general inhibitor of nitric oxide synthase, was also applied to test the inhibition of NO concentration. We found that SBPs were significantly lower in telmisartan therapy group than in placebo treated hypertensive rats and WKYs (p<0.05). The NO concentration was significantly higher in telmisartan-treated group with increased activity of the PI3K/Akt pathway and activated eNOS signaling. Blockade of Akt activity reversed such effects. Activation of AMPK also contributed to the phosphorylation of eNOS. L-NMMA treatment reduced less NO concentration in SHR rats than the telmisartan co-treated groups. Oxidative stress in SHRs was also attenuated by telmisartan administration, shown by reduced formation of nitrotyrosine, 8-isoprostane, and recovered SOD protein level. Telmisartan enhanced NO release by activating the PI3K/Akt system, AMPK phosphorylation and eNOS expression, which attenuated the blood pressure and oxidative stress in SHRs., L. Xu, Y. Liu., and Obsahuje seznam literatury
Advanced glycation end products (AGEs) may play an important adverse role in process of atherosclerosis, diabetes, aging and chronic renal failure. Levels of Ne-carboxymethyllysine and fluorescent AGE values were estimated in two nutritional population groups - alternative group (vegetarians - plant food, milk products, eggs) and traditional group (omnivorous subjects). Vegetarians have a significantly higher carboxymethyllysine content in plasma and fluorescent AGE values. Intake of proteins, lysine and monosaccharides as well as culinary treatment, consumption of food AGEs (mainly from technologically processed products) and the routes of Maillard reaction in organism are the substantial sources of plasma AGEs. Vegetarians consume less proteins and saccharides. Lysine intake is significantly reduced (low content in plant proteins). Subjects on alternative nutrition do not use high temperature for culinary treatment and consume low amount of technologically processed food. Fructation induced AGE fluorescence is greater as compared with that induced by glucose. It is due to higher participation of a more reactive acyclic form of fructose. Intake of vegetables and fruit with predominance of fructose is significantly higher in vegetarians. Comparison of nutrition and plasma AGEs in vegetarian and omnivorous groups shows that the higher intake of fructose in alternative nutrition of healthy subjects may cause an increase of AGE levels., M. Krajčovičová-Kudláčková, K. Šebeková, R. Schinzel., and Obsahuje bibliografii
Accelerated glycoxidation takes part in the development of diabetic complications. We determined advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP) in the sera of 52 patients with diabetes mellitus (DM) - 18 with DM Type 1 and 34 with DM Type 2 and examined their relationship to the compensation of the disease. AGEs were estimated spectrofluorimetrically (350 nm/440 nm) whereas AOPP were determined spectro-photometrically (340 nm). AGEs were elevated only in DM Type 2 (DM2 5.11±1.15x103 AU/g vs controls 4.08±0.71x103 AU/g, p<0.001, vs DM1 4.14±0.86x103 AU/g, p<0.005, DM1 vs controls were not significant). AOPP were elevated significantly in both types of DM with higher levels in DM Type 2 (DM2 157.50±75.15 mmol/l vs healthy subjects 79.80±23.72 mmol/l, p<0.001, vs DM1 97.50±30.91 mmol/l, p<0.005, DM1 vs controls p<0.05). There was a tight correlation between AGEs and AOPP in both types of DM (DM1 r=0.75, DM2 r=0.47 (p<0.05)) and both AGEs and AOPP correlated with triglycerides. In DM Type 1 only, AGEs correlated with HbA1c r=0.47 (p<0.05) and with blood glucose. Slight but not significant differences in AGEs and AOPP levels were observed in patients with or without diabetic complications. Oxidative stress is increased in both types of DM, more in Type 2 where it contributes to the formation of glycoxidation products., M. Kalousová, J. Škrha, T. Zima., and Obsahuje bibliografii
Altered Ca2+ handling may be responsible for the development of cardiac contractile dysfunctions with advanced age. In the present study, we investigated the roles of oxidative damage to sarcoplasmic reticulum (SR) and expression of Ca2+-ATPase (SERCA 2a) and phospholamban in age-associated dysfunction of cardiac SR. SR vesicles were prepared from hearts of 2-, 6-, 15-, and 26-month-old Wistar rats. Although activity of Ca2+-ATPase decreased with advancing age, no differences in relative amounts of SERCA 2a and phospholamban protein were observed. On the other hand, significant accumulation of protein oxidative damage occurred with aging. The results of this study suggest that agerelated alteration in Ca2+-ATPase activity in the rat heart is not a consequence of decreased protein levels of SERCA 2a and phospholamban, but could arise from oxidative modifications of SR proteins. Cellular oxidative damage caused by reactive oxygen species could contribute to age-related alternations in myocardial relaxation., E. Babušíková ... [et al.]., and Obsahuje seznam literatury
a1_Fifty years ago, Lewis K. Dahl has presented a new model of salt hypertension – salt-sensitive and salt-resistant Dahl rats. Twenty years later, John P. Rapp has published the first and so far the only comprehensive review on this rat model covering numerous aspects of pathophysiology and genetics of salt hypertension. When we summarized 25 years of our own research on Dahl/Rapp rats, we have realized the need to outline principal abnormalities of this model, to show their interactions at different levels of the organism and to highlight the ontogenetic aspects of salt hypertension development. Our attention was focused on some cellular aspects (cell membrane function, ion transport, cell calcium handling), intra- and extrarenal factors affecting renal function and/or renal injury, local and systemic effects of reninangiotensin-aldosterone system, endothelial and smooth muscle changes responsible for abnormal vascular contraction or relaxation, altered balance between various vasoconstrictor and vasodilator systems in blood pressure maintenance as well as on the central nervous and peripheral mechanisms involved in the regulation of circulatory homeostasis. We also searched for the age-dependent impact of environmental and pharmacological interventions, which modify the development of high blood pressure and/or organ damage, if they influence the saltsensitive organism in particular critical periods of development (developmental windows). Thus, severe self-sustaining salt hypertension in young Dahl rats is characterized by pronounced dysbalance between augmented sympathetic hyperactivity and relative nitric oxide deficiency, attenuated baroreflex as well as by a major increase of residual blood pressure indicating profound remodeling of resistance vessels. Salt hypertension development in young but not in adult Dahl rats can be attenuated by preventive increase of potassium or calcium intake., a2_On the contrary, moderate salt hypertension in adult Dahl rats is attenuated by superoxide scavenging or endothelin-A receptor blockade which do not affect salt hypertension development in young animals., J. Zicha, ... [et al.]., and Obsahuje seznam literatury
The aim of the study was to investigate age-related changes in postural responses to platform translation with 3 various velocities. We focused on the influence of linear velocity using the smoothed profile of platform acceleration (till 100 cm.s−2 ). Eleven healthy young (20-31 years) and eleven healthy elderly (65-76 years) subjects were examined. The subjects stood on the force platform with their eyes closed. Each trial (lasting for 8 sec) with different velocity (10, 15, 20 cm.s−1 ) of 20 cm backward platform translation was repeated 4 times. We have recorded displacements of the centre of pressure (CoP) and the EMG activity of gastrocnemius muscle (GS) and tibialis anterior muscle (TA). The results showed increased maximal values of CoP responses to the platform translation. There was also observed a scaling delay of CoP responses to platform translation with different velocities in elderly. The EMG activity of GS muscle during backward platform translation was of about similar shape in both groups during the slowest platform velocity, but it increased depending on rising velocity. EMG activity of TA was not related to the platform velocity. Early parts of postural responses showed significant co-activation of TA and GS muscles of elderly. It is likely that elderly increased body stiffening in order to help their further balance control., Z. Halická ... [et al.]., and Obsahuje seznam literatury