We studied the effects of long-term administration of molsidomine and pentaerythrityl tetranitrate (PETN) on the cardiovascular system of spontaneously hypertensive rats (SHR). One control and three experimental groups of 10-week-old animals were used: 1) control Wistar rats, 2) SHR, 3) SHR treated with molsidomine in tap water (100 mg/kg/day, by gavage), and 4) SHR treated with PETN in tap water (200 mg/kg/day, by gavage). After six weeks, the content of cGMP in platelets and NO synthase (NOS) activity in aortas were evaluated in the experimental groups. For morphological evaluation the rats were perfused at 120 mm Hg with a glutaraldehyde fixative and the arteries were processed for electron microscopy. Blood pressure and heart weight/body weight ratio (HW/BW) were increased in all experimental groups with respect to the controls. HW/BW was lower in the molsidomine group in comparison to both SHR and PETN-treated group. The platelet content of cGMP was increased and the activity of NOS in the aortas was decreased in the molsidomine and PETN-treated groups. Wall thickness and cross-sectional area of thoracic aorta, carotid artery and coronary artery were increased similarly in all experimental groups compared to the controls, but there were no differences among the experimental groups. We summarize that long-term administration of exogenous NO donors did not improve pathological changes of the cardiovascular system in SHR., F. Kristek, V. Fáberová, I. Varga., and Obsahuje bibliografii
To determine whether the exposure to long term enriched environment (EE) would result in a continuous improvement of neurological recovery and ameliora te the loss of brain tissue after traumatic brain injury (TBI) vs. standard housing (SH). Male Sprague-Dawley rats (300-350 g, n=28) underwent lateral fluid percussion brain injury or SHAM operation. One TBI group was held under complex EE for 90 days, the other under SH. Neuromotor and sensorimotor dysfunction and recovery were assessed after injury and at days 7, 15, and 90 via Composite Neuroscore (NS), RotaRod test, and Barnes Circular Maze (BCM). Cortical tissue loss was assessed using serial brain sections. After day 7 EE animals showed similar latencies and errors as SHAM in the BCM. SH animals performed notably worse with differences still significant on day 90 (p<0.001). RotaRod test and NS revealed superior results for EE animals after day 7. The mean cortical volume was significantly higher in EE vs. SH animals (p=0.003). In summary, EE animals after lateral fluid percussion (LFP) brain injury performed sign ificantly better than SH animals after 90 days of recovery. The window of opportunity may be wide and also lends further credibility to the importance of long term interventions in patients suffering from TBI., M. Maegele, M. Braun, A. Wafaisade, N. Schäfer, M. Lippert-Gruener, C. Kreipke, J. Rafols, U. Schäfer, D. N. Angelov, E. K. Stuermer., and Obsahuje bibliografii
Little is known about the effect of chronic angiotensin-converting enzyme inhibition on the catecholamine levels in fowls. In this study, we investigated the effects of chronic lisinopri1 dihydrate (Ld) application on the plasma levels of adrenaline and noradrenaline and on the blood pressure. Lisinopril was given in different concentrations (25, 75 and 250 mg/l drinking water) to the white Leghorn chickens for 9 weeks, while the control group drank tap water only. Twenty-eight hours after the last lisinopril application, arterial blood pressure (BP), plasma adrenaline and noradrenaline levels, plasma renin (PRA) and plasma angiotensin-converting enzyme (ACE) activities were determined. In all concentrations, lisinopril significantly increased PRA and decreased ACE activities. Arterial BP was decreased only in the group receiving high lisinopril concentration (Controls 119±10.27, Ld3 98±5.4 mm Hg). However, the lower lisinopril concentrations did not alter arterial BP compared to the control group. Plasma noradrenaline levels were decreased in a concentration-dependent manner (47-58 %), but plasma adrenaline levels remained unchanged. The heart weight/body weight ratio was not changed in any of the lisinopril-treated groups. The persistent decrease in the blood pressure after lisinopril treatment was not directly related to a decrease of plasma ACE activity or plasma noradrenaline levels. Its mechanism still remains to be elucidated., H. S. Ozdemir, H. E. Aksulu, F. Karataş, B. Ustündag, I. Bingöl., and Obsahuje bibliografii
Advanced atherosclerotic changes can often resist even to very aggressive treatment. Although basic mechanisms of its origin and development are known, some important steps in this process are still waiting for more detailed explanation. Therefore, in addition to already proved aggressive lowering of LDL cholesterol, appropriate timing of atherosclerosis treatment is of the essence. Revealing different stages of atherosclerotic process, less or more sensitive to treatment is of primary importance; however, its detection is complicated by several facts including not exactly identifiable periods of quiescence and progression of atherosclerotic process. One of populations, study of which could add valuable information regarding this problem , are women in menop ausal transition. Previously unsuccessful therapy with hormone replacement therapy is restudied with focus on the time of/after menopause. Now, it is supposed to be favorable in women soon, approximately less than 8 years, after menopause. In addition, the same principle - optimal timing of the intervention of traditional cardiovascular risk factors, especially lipids, could be also of importance. Therefore, menopausal transition could be optimal period for the intervention in women at risk. However, this a pproach is to be proved by evidence from controlled prospective studies focused on lifestyle and/or pharmacological intervention., J. Piťha., and Obsahuje bibliografii
Domoic acid (DA) is a potent marine neurotoxine present in seafood. Intoxication by DA causes gastrointestinal symptoms like vomiting and diarrhoea and also the so-called amnesic shellfish poisoning (inflicting memory impairment and seizures). Since exposure to non-convulsive doses is relevant to the human health, we investigated the effect of low dose DA administration in adult Wistar rats. Rats were administered with DA at the dose 1.0 mg/kg and their behavior was monitored for one hour in three sessions. The first session started immediately after DA administration. The second and third session started one and two weeks later. After the third session, the histochemical analysis of the hippocampi of the animals was conducted (Fluoro-Jade B, bis-benzimide). DA increased time spent by locomotion and distance travelled in the second half of the first session and this effect was pronounced during the second and third session. Exploratory rearing was decreased by DA administration in the first half of the first session. DA influenced the grooming in biphasic manner (decrease followed by an increase of time spent by grooming). This biphasic trend was observed even two weeks after the DA administration. Histochemistry of DA treated rats did not confirm the presence of apoptotic bodies, Fluoro-Jade B positive cells were not found neither in CA1 nor CA3 area of the hippocampi. Our study revealed that a low dose of DA affect short and long-term the spontaneous behavior of rats without inducing neuronal damage., M. Schwarz, K. Jandová, I. Struk, D. Marešová, J. Pokorný, V. Riljak., and Obsahuje bibliografii
a1_The effect of low-salt diet on phospholipid composition and remodeling was examined in rat colon which represents a mineralocorticoid target tissue. To elucidate this question, male Wistar rats were fed a low-salt diet and drank distilled water (LS, low-salt group) or saline instead of water (HS, high-salt group) for 12 days before the phospholipid concentration and fatty acid composition of isolated colonocytes were examined. The dietary regimens significantly influenced the plasma concentration of aldosterone which was high in LS group and almost zero in HS group. Plasma concentration of corticosterone was unchanged. When expressed in terms of cellular protein content, a significantly higher concentration of phospholipids was found in LS group, with the exception of sphingomyelin (SM) and phosphatidylserine (PS). Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) accounted for more than 70 % of total phospholipids in both groups. A comparison of phospholipid distribution in LS and HS groups demonstrated a higher percentage of PE and a small, but significant, decrease of PC and SM in LS group. The percentage of phosphatidylinositol (PI), PS and cardiolipin (CL) were not affected by mineralocorticoid treatment. With respect to the major phospholipids (PE, PC), a higher level of n-6 polyunsaturated fatty acids (PUFA) and lower levels of monounsaturated fatty acids were detected in PC of LS group. The increase of PUFA predominantly reflected an increase in arachidonic acid by 53%. In comparison to the HS group, oleic acid content was decreased in PC and PE isolated from colonocytes of the LS group. Our data indicate that alterations in phospholipid concentration and metabolism can be detected in rats with secondary hyperaldosteronism., a2_The changes in phospholipid concentration and their fatty acid composition during fully developed effect of low dietary Na+ intake may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function., L. Mrnka, O. Nováková, F. Novák, E. Tvrzická , J. Pácha., and Obsahuje bibliografii
Hypokalemia as a typical feature of primary aldosteronism (PA) is associated with muscle weakness and could contribute to lower cardio pulmonary fitness. The aim of this study was to describe cardiopulmonary fitness and exercise blood pressure and their determinants during a symptom-limited exercise stress test in patients with PA. We performed a cross-sectional study of patients with confirmed PA who were included before adrenal vein sampling on whom a symptom-limited exercise stress test with expired gas analysis was performed. Patients were switched to the treatment with doxazosin and verapamil at least tw o weeks befor e the study. In 27 patients (17 male) the VO 2peak was 25.4± 6.0 ml/k g/min which corresponds to 80.8 ±18.9 % of Czech national norm. Linear regression analysis shows that VO 2peak de pends on doxazosin dose (DX) (p=0.001) and kal emia (p= 0.02): VO 2peak = 4.2 - 1.0 * DX + 7.6 * Ka lemia. Patients with higher doxazosin doses had a longer history of hypertension and had used more antihypertensives before examination, thus indicating that VO 2peak also depends on the severity of hypertension. In patients with PA, lower cardiopulmonary fitness depends inversely on the severity of hypertension and o n lower plasma potassium level., V. Tuka, M. Matoulek, T. Zelinka, J. Rosa, O. Petrák, O. Mikeš, Z. Krátká, B. Štrauch, R. Holaj, J. Widimský Jr., and Obsahuje bibliografii
Vaccines have helped considerably in eliminating some lifethreatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world’s most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature., G. Mužíková, R. Laga., and Obsahuje bibliografii
Atherosclerosis pathology is the interplay between high intrav ascular LDL particle concentration and monocyte/ macrophage presence within the sub -endothelial space of the artery. In this project, phenotypes of macrophages connected with subclinical inflammation in adipose tissue of living kidney donors were studied. Samples of subcutaneous adipose tissue of living kidney donors (n=36) were exposed to collagenase. Stromal vascular fraction (SVF) was eluted from the samples, then labeled with monoclonal antibodies (anti- CD14 and anti -calprotectin), conjugated with fluo rochromes and analy zed by flow cytometry. The positive correlation between the number of total macrophages and calprotectin- positive macrophages with BMI in the subcutaneous adipose tissue of postmenopausal women was demonstrated (p<0.05; R=0.43 and p<0.01 ; R=0.60), whereas no positive correlation in premenopausal women and men was shown. In conclusion, we documented a significant effect of BMI increase on the presence of total macrophages in adipose tissue of postmenopausal women, in contrast to premenopausal women. This difference was much more pronounced when proinflammatory macrophages with membrane- bound calprotectin were analyzed., A. Králová, I. Králová Lesná, J. Froněk, S. Čejková, A. Sekerková, L. Janoušek, F. Thieme, I. Stříž, J. Ždychová, R. Poledne., and Obsahuje bibliografii
Apolipoprotein (apo) B-100 is a key protein compound of plasma lipid metabolism. This protein, as a sole component of LDL particles, to a great extent controls the homeostasis of LDL cholesterol in the plasma. Therefore, this protein and its structural variants play an important role in development of hyperlipidemia and atherosclerosis. Intensive research into the structure and biological functions of apoB-100 has led to identification of its complete structure as well as the responsible binding sites. With the development of the methods of molecular biology, some structural variants of the apoB-100 protein that directly affect its binding properties have been described. These are mutations leading to amino acid substitution at positions 3500 (R3500Q and R3500W) and 3531 (R3531C) that have been shown to decrease the binding affinity of apoB-100 in vitro. However, only the former mutations have been unequivocally demonstrated to cause hyperlipidemia in vivo. This minireview is aimed to discuss the impact of apoB-100 and its structural variants on plasma lipid metabolism and development of hyperlipidemia., M. Vrablík, R. Češka, A. Hořínek., and Obsahuje bibliografii