Cardiovascular (CV) mortality was reduced more than 50 % in the Czech population at the turn of the century, due to an improvement of major CV risk factors in the general population, interventional procedures implemented into the treatment of acute coronar y events, and new drugs (ACE inhibitors, statins etc.) for CV prevention (Czech MONICA and post-MONICA studies, 1985-2008). An insufficient level of preventive efforts is described in the Czech patients after acute coronary syndrome (Czech part of the EURO ASPIRE studies, 1995-2013). Drug underdosing and wrong patients’ compliance to life style and drug therapy recommendations represent two main reasons of this unsatisfactory situation. The residual vascular risk of patients with stable coronary heart diseas e (CHD) is still high due to a poor control of conventional risk factors on the one hand, and due to increasing weight and glucose metabolism abnormalities on the other hand. Patients with insulin resistance and glucose dis orders have more frequently non-LDL-C dyslipidemia (atherogenic dyslipidemia), hypertriglyceridemic waist and high atherogenic index of plasma (AIP>0.24), i.e. markers of residual CV risk. Among others increased dose of statins and combined lipid modifying therapy should be implemented in patients with CHD, diabetes or metabolic syndrome., H. Rosolová, B. Nussbaumerová, O. Mayer Jr., R. Cífková, J. Bruthans., and Obsahuje bibliografii
Drugs interfering with the renin-angiotensin-aldosterone system (RAAS) improved the prognosis in patients with hypertension, heart failure, diabetes and chronic kidney disease. However, combining different drugs brought no further benefit while increasing the risk of hyperkalemia, hypotension and acute renal failure. This was so with combining angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptors type 1 antagonists (ARB). Dissimilarly, in animal disease models this dual therapy proved clearly superior to single drug treatment and became the optimal standard regime for comparison with other treatments. This review analyzes the causes of the discrepancy of effects of the dual therapy between animal experiments versus clinical studies, and is focused on the outcomes in chronic kidney disease. Discussed is the role of species differences in RAAS, of the variability of the disease features in humans versus relative stability in animals, of the genetic uniformity in the animals but not in humans, and of the biased publication habits of experimental versus clinical studies. We attempt to understand the causes and reconcile the discordant findings and suggest to what extent dual RAAS inhibition should be continued in animal experiments and why its application in the clinics should be limited to strictly selected groups of patients., V. Čertíková Chábová, L. Červenka., and Obsahuje bibliografii
T-2 toxin and its metabolite HT-2 toxin are one of the most toxic mycotoxins of type A-trichothecenes, which are produced mainly by Fusarium species. Therefore, study of Fusarium toxins T-2 toxin and HT-2 toxin is an essential issue because they could also play role in failures of reproductive functions as well as endocrine system of domestic animals. Assessment of the effect of A-trichothecene mycotoxin HT-2 toxin alone or combined with insulin-like growth factor (IGF-I), leptin and ghrelin on estradiol secretion by rabbit ovarian fragments in vitro was done. Rabbit ovarian fragments were incubated without (control group) or with HT-2 toxin, or its combinations with IGF-I, leptin and ghrelin at various concentrations for 24 h. Secretion of 17β-estradiol was determined by ELISA. Firstly, HT-2 toxin at the doses 10 and 100 ng.ml-1, but not at 1 ng.ml-1 decreased 17β-estradiol secretion by ovarian fragments. Secondly, 17β-estradiol secretion was not affected by HT-2 toxin exposure combined with growth factor IGF-I, metabolic hormones leptin and ghrelin. In conclusion, HT-2 toxin has potent direct dose-dependent effects on ovarian steroidogenesis in rabbits. These direct effects of HT-2 mycotoxin on ovarian steroidogenesis could impact negatively on the reproductive performance of rabbits., A. Kolesarova, N. Maruniakova, A. Kadasi, M. Halenar, M. Marak, A. V. Sirotkin., and Obsahuje bibliografii
Fat-enriched diet is strongly associated with cataract development. Laurus nobilis shows antioxidant activity. Herein we evaluated the effect of Laurus nobilis oral administration on the blood and lenses antioxidant activity in rabbits under fat-enriched diet. Sixty rabbits divided into 4 groups were used. One group represented the control (N-CTR). The second group (P-CTR) fed a diet supplemented with 2.5 % of pig fat; the third group (EXP1) received a diet supplemented with 2.5 % of pig fat and 1 g/kg of dried-bay leaves; the fourth group (EXP2) was treated with dried-bay leaves at the rate of 1 g/kg of feed. At baseline and at the end of the study (56 days) the following blood parameters were determined: thiobarbituric acid reactive substances (TBARS), reactive oxygen metabolites (ROMs), total phenols, superoxide dismutase (SOD), oxygen radical absorbance capacity (ORACpca), ferric ion reducing antioxidant power (FRAP), retinol and alfa-tocopherol. At the end of the follow-up, the eyes were enucleated and the antioxidant profile, such as total antioxidant activity (TAC), TBARS, retinol and alfa-tocopherol of lenses was evaluated. Plasma ROMs and TBARS levels were statistically lower in the groups receiving bay leaves integration. A significant increase of plasma retinol, FRAP and ORACpca levels was found in EXP1 and EXP2 groups, whereas plasma alfa-tocopherol resulted statistically higher only in EXP2 group. Bay leaves supplementation enhanced TAC, retinol and alfa-tocopherol in rabbit lens, particularly in EXP2 group; whereas lenses TBARS levels significantly decreased in both treated groups. These findings demonstrate that Laurus nobilis oral administration exerts a protective effect on the risk of cataract development in rabbits under fat-enriched diet., D. Casamassima, F. Chiosi, F. Vizzarri, M. Palazzo, C. Costagliola., and Obsahuje bibliografii
Previous studies have suggested that the Notch signaling pathway plays a very important role in the proliferation and differentiation of pulmonary microvascular endothelial cells (PMVECs). Therefore, we aimed to investigate the expression level of Notch-related signaling molecules in PMVECs in bleomycin (BLM)-induced rat pulmonary fibrosis. Immunohistochemistry, immunofluorescence, Western blotting, and real-time PCR were used to analyze the differences in protein and mRNA expression levels of Notch-related signaling molecules, i.e. Notch1, Jagged1, Delta-like ligand 4 (Dll4), and hairy and enhancer of split homolog 1 (Hes1), between a control group treated with intratracheal instillation of saline and a study group treated with intratracheal instillation of BLM solution. Expression levels of the receptor Notch1 and one of its ligands, Jagged1, were upregulated, while the expression levels of the ligand Dll4 and the target molecule of the Notch signaling pathway, Hes1, were downregulated. The differences in protein and mRNA expression levels between the control and study groups were significant (p<0.001). The Jagged1/Notch1 signaling pathway is activated in the pathogenesis of BLM-induced rat pulmonary fibrosis, while the Dll4/Notch1 signaling pathway is inhibited, which inhibits the suppressive effect of Dll4/Notch1 signaling on PMVEC overproliferation, further causing PMVEC dysfunction in cell sprouting and maturation as well as abnormal differentiation of the cell phenotype. Conversely, the downexpression of Hes1 indicates that the Jagged1/Notch1 signaling pathway could be a non-canonical Notch signaling pathway independent of Hes1 activation, which differs from the canonical Dll4/Notch1 signaling pathway., Q. Yin, W. Wang, G. Cui, H. Nan, L. Yan, W. Zhang, S. Zhang, J. Wei., and Obsahuje bibliografii
Adenine-induced model of chronic kidney disease (CKD) is a widely used model especially in studies testing novel nephroprotective agents. We investigated the effects of adenineinduced CKD in rats on the activities of some xenobiotic metabolizing enzymes in liver and kidneys, and on some in vivo indicators of drug metabolism (viz pentobarbitone sleeping time, and plasma concentration of theophylline 90 min post administration). CKD was induced by orally feeding adenine (0.25 % w/w) for 35 days. Adenine induced all the characteristics of CKD, which was confirmed by biochemical and histological findings. Glutathione concentration and activities of some enzymes involved in its metabolism were reduced in kidneys and livers of rats with CKD. Renal CYP450 1A1 activity was significantly inhibited by adenine, but other measured isoenzymes (1A2, 3A4 and 2E1) were not significantly affected. Adenine significantly prolonged pentobarbitone-sleeping time and increased plasma theophylline concentration 90 min post administration. Adenine also induced a moderate degree of hepatic damages as indicated histologically and by significant elevations in some plasma enzymes. The results suggest that adenine-induced CKD is associated with significant in vivo inhibitory activities on some drug-metabolizing enzymes, with most of the effect on the kidneys rather than the liver., M. Al Za’abi, A. Shalaby, P. Manoj, B. H. Ali., and Obsahuje bibliografii
Smoking is the most widespread substance dependence in the world. Nicotine and some other components of the cigarette smoke cause various endocrine imbalances, and have negative effects on pituitary, thyroid, adrenal, testicular and ovarian functions. Here, we examined studies that describe the influence of smoking and smoking cessation on the male and female reproductive systems. We also focused on studies providing an account of differences in cessation success rates between men and women. In men, the most common effects associated with smoking are erectile dysfunction and decreasing spermiogram quality. Several groups have studied the effects of cigarette smoking on testosterone levels in men. However, the results have been conflicting. In women, nicotine has an antiestrogen effect and increases the ratio of androgens to estrogens throughout life. Beside nicotine, other cigarette toxins also cause dysregulation of reproductive and hormonal system, and essentially influence the probability of a successful pregnancy not only in cases of assisted reproduction but also in healthy women. Tobacco addiction is one of the forms of addiction that are generally thought to be different for men and for women. Women are less successful than men in quitting smoking, and nicotine replacement therapy is less effective in female smokers. We also summarize recent studies that have indicated possible reasons., H. Jandíková, M. Dušková, L. Stárka., and Obsahuje bibliografii
Nearly 60 years has elapsed since the first isolation and identification of 7α-hydroxy-dehydroepiandrosterone, and in that time much information has been gained on its occurrence, metabolism, ontogeny, immunomodulatory activity, cell proliferation, cortisol control in local tissues and neuroactivity. Additional knowledge about this steroid may elucidate its role in obesity, neurodegenerative disturbances such as Alzheimer’s disease, or psychiatric disorders such as schizophrenia or depression. This review aims to provide a comprehensive summary of the available literature on 7α-hydroxydehydroepiandrosterone., L. Stárka., and Obsahuje bibliografii
Ferritin and increased iron stores first appea red on the list of cardiovascular risk factors more than 30 years ago and their causal role in the pathogenesis of atherosclerosis has been heavily discussed since the early 1990s. It seems that besides traditional factors such as hyperlipoprotein emia, hyp ertension, diabetes mellitus, obesity, physical inactivity, smoking and family history, high iron stores represent an additional parameter that could modify individual cardiovascular risk. The role of iron in the pathogenesis of atherosclerosis was origina lly primarily associated with its ability to cataly ze the formation of highly reactive free oxygen radicals and the oxidation of atherogenic lipoproteins. Later, it became clear that the mechanism is more complex. Atherosclerosis is a chronic fibroprolife rative inflammatory process and iron, through increased oxidation stress as well as directly, can control both native and adaptive immune responses. Within the arterial wall, iron affects all of the cell types that participate in the atherosclerotic proces s (monocytes/macrophages, endothelial cells, vascular smooth muscle cells and platelets). Most intracellular iron is bound in ferritin, whereas redox-active iron forms labile iron pool. Pro-inflammatory and anti-inflammatory macrophages within arterial plaque differ with regard to the amount of intracellular iron and most probably with regard to their labile iron pool. Yet, the relation between plasma ferritin and intracellular labile iro n pool has not been fully clarified. Data from population studies document that the consumption of meat and lack of physical activity contribute to increased iron stores. Patients with hereditary h emochromatosis, despite extreme iron storage, do not show i ncreased manifestation of atherosclerosis probably due to the low expression of hepcidin in macrophages., P. Kraml., and Obsahuje bibliografii
Dental management behavior problems are thought to be both multifactorial and multidimensional, consisting of physiological, behavioral and cognitive components. The stress response to pain or even the anticipation of distress initiates activation of the hypothalamic-pituitary-adrenal axis and causes an increase of cortisol and catecholamines. The literature on the role of hormones in dental management behavior problems comprises about one hundred papers, which have mainly been focused on this activation of the HPA axis in various situations in dental care. They have generally used salivary cortisol as a marker of the activity of the HPA axis, sometimes combined with salivary alpha amylase. Here we summarize the literature data on the role of stress hormones in dental management behavior problems., M. Dušková, J. Vašáková, J. Dušková, J. Kaiferová, Z. Broukal, L. Stárka., and Obsahuje bibliografii