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
Polyunsaturated omega-3 fatty acids ( ω-3 PUFA) are important components of cell membrane a ffecting its function and their deficiency is deleterious to health. We have previously shown that spontaneously hypertensive rats (SHR) are prone to life- threatening arrhythmias that are reduced by ω-3 PUFA intake. Purpose of this study was to explore plasma and red blood cells (RBC) profile of ω-3 and ω-6 PUFA as well as to determine ω-3 index, a risk factor for sudden cardiac death, in aged SHR and the effect of ω-3 PUFA intake. Male and female 12-month-old SHR and age-matched Wi star rats fed with ω-3 PUFA (200 mg/kg BW/day/2 month) were compared with untreated rats. Composition of ω-3 PUFA: alfa linolenic acid, eicosapentaenoic acid (EPA) and docosahexaen oic acid (DHA) as well as ω-6 PUFA: linoleic acid and arachidonic acid was analyzed by gas chromatography. Results showed sex- and strain-related differences of basal ω-3 and ω-6 PUFA levels in plasma and RBC as well as in response to ω-3 PUFA intake. Comparing to Wistar rats ω-3 index, expressed as a percentage of EPA+DHA of total fatty acids, was lower in SHR and it increased due to consumption of ω-3 PUFA. Findings support our hypothesis that lower ω-3 index may be also a marker of increased propensity of the hypertensive rat heart to malignant arrhythmias., B. Bačová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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
In this study we compared the levels of interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α) in population samples characterized by a high or low level of self-reported depression. We measured serum IL-6, IL-8, IL-10 and TNF-α in two cohorts which differed in scoring on the Zung Self-Rating Depression Scale (ZSDS). The group with a high score in ZSDS (average SDS index = 62.9) was called DEP (n=27), the group with a low score in ZSDS (average SDS index = 29.9) was called NDEP (n=16). The groups did not significantly differ in age, waist circumference and body mass index. For the assessment of serum cytokine levels multiplex immunoanalytic xMAP(LUMINEX) technology was used. We found lower IL-6 in the DEP group (medians; DEP 4.08 pg/ml vs. NDEP 6.11 pg/ml) on the border of statistical significance in multiple regression analysis (p=0.049). Serum levels of all other studied cytokines were not significantly different (medians; IL-8: DEP 2.18 pg/ml vs. NDEP 2.61 pg/ml; IL-10: DEP 2.85 pg/ml vs. NDEP 2.94 pg/ml; TNF-α: DEP 2.32 pg/ml vs. NDEP 2.30 pg/ml). These results are in contradiction to the prevailing opinion that proinflammatory cytokine levels are elevated in people with symptoms of depression. and Obsahuje bibliografii a bibliografické odkazy
Arterial sites with low wall shear stress (WSS) are more prone to the development of atherosclerotic plaques, as was observed in carotid arteries in subjects with atherosclerosis risk factors. Type 2 diabetes mellitus (DM), hypertension, hyperlipidemia and other components of the metabolic syndrome, are associated with high risk for symptomatic cerebrovascular disease. It was shown by others that untreated type 2 DM is associated with lower WSS in common carotid arteries. However, the cardiovascular risk of type 2 DM could be modified by therapy. The aim of our study was to test the hypothesis that treated type 2 DM subjects with metabolic syndrome still have lower WSS in common carotid arteries than healthy controls. We enrolled 26 compensated DM subjects with metabolic syndrome, treated by metformin, statins and ACEI for more than 6 months, and 22 aged-comparable healthy controls. Wall shear rate (WSR) was used as a measure of WSS. A linear 3-11 MHz probe was used to measure blood velocity and internal diameter in the common carotid arteries. We compared observed values of WSR adjusted for age by ANCOVA. Wall shear rate was significantly lower in DM group than in control subjects: peak (systolic) values of wall shear rate were 410±130 s-1 vs. 487±111 s-1 (p<0.005). DM subjects had significantly lower WSR, because of both thinner lumen and slower blood flow velocities. Lower WSR was accompanied by higher IMT (0.73±0.12 mm vs. 0.64±0.11 mm, p<0.001). Treated subjects with compensated type 2 DM with metabolic syndrome still have atherogenic hemodynamic profile. These findings might help to understand faster progression of atherosclerosis in diabetic subjects with metabolic syndrome despite up-to-date medication., E. Chytilová ...[et al.]., and Obsahuje seznam literatury
Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries. Mast cells have an important role in many inflammatory diseases and they are also involved in tissue remodeling. Tissue hypoxia is associated with mast cell activation and the release of proteolytic enzymes, angiogenic and growth factors which mediate tissue destruction and remodeling in a variety of physiological and pathological conditions. Here we focused on the role of mast cells in the pathogenesis of hypoxic pulmonary hypertension from the past to the present., H. Maxová, J. Herget, M. Vízek., and Obsahuje seznam literatury
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
Obesity is linked to a low-level chronic inflammatory state that may contribute to the development of associated metabolic complications. Retinol-binding protein 4 (RBP4) is an adipokine associated with parameters of obesity including insulin resistance indices, body mass index, waist circumference, lipid profile, and recently, with circulating inflammatory factors. Due to the infiltration of adipose tissue in obesity by macrophages derived from circulating monocytes and, on the other hand, the existence of a close genetic relationship between adipocytes and macrophages, we decided to examine if RBP4 is expressed in monocytes and/or primary human macrophages. While we did not detect expression of RBP4 in undifferentiated monocytes, RBP4 expression became evident during the differentiation of monocytes into macrophages and was highest in differentiated macrophages. Once we demonstrated the expression of RBP4 in macrophages, we checked if RBP4 expression could be regulated by inflammatory stimuli such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), or the endotoxin lipopolysaccharide (LPS). We observed that while RBP4 expression was strongly inhibited by TNF-α and LPS, it was not affected by IL-6. Our results highlight the complexity behind the regulation of this adipokine and demonstrate that RBP4 expression in macrophages could be modulated by inflammatory stimuli., M. Broch ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy