Non-surgical management of aortic valve disease has been given considerable attention. Several recent publications have already reported its use in clinical practice. The main issue is to get an understanding of the pathophysiological processes and, most importantly, extensive experimental activity. In addition to testing various animal models, technical and material aspects are also being intensively investigated. It is not clear yet whether the durability and applicability of this promising development will be comparable with the standard of current cardiac surgery. Nonetheless, even the use of some models as a temporary approach helping to improve the circulatory status, not allowing safe surgery, is certainly justified. At any rate, a new stage of research and clinical application has been set off. However, experimental background continues to be simply indispensable. The paper is a short review of the issue., J. Šochman, J. H. Peregrin., and Obsahuje bibliografii a bibliografické odkazy
The development of the cauda equina syndrome in the dog and the involvement of spinal nitric oxide synthase immunoreactivity (NOS-IR) and catalytic nitric oxide synthase (cNOS) activity were studied in a pain model caused by multiple cauda equina constrictions. Increased NOS-IR was found two days post-constriction in neurons of the deep dorsal horn and in large, mostly bipolar neurons located in the internal basal nucleus of Cajal seen along the medial border of the dorsal horn. Concomitantly, NOS-IR was detected in small neurons close to the medioventral border of the ventral horn. High NOS-IR appeared in a dense sacral vascular body close to the Lissauer tract in S1-S3 segments. Somatic and fiber-like NOS-IR appeared at five days post-constriction in the Lissauer tract and in the lateral and medial collateral pathways arising from the Lissauer tract. Both pathways were accompanied by a dense punctate NOS immunopositive staining. Simultaneously, the internal basal nucleus of Cajal and neuropil of this nucleus exhibited high NOS-IR. A significant decrease in the number of small NOS immunoreactive somata was noted in laminae I-II of L6-S2 segments at five days post-constriction while, at the same time, the number of NOS immunoreactive neurons located in laminae VIII and IX was significantly increased. Moreover, high immunopositivity in the sacral vascular body persisted along with a highly expressed NOS-IR staining of vessels supplying the dorsal sacral gray commissure and dorsal horn in S1-S3 segments. cNOS activity, based on a radioassay of compartmentalized gray and white matter regions of lower lumbar segments and non-compartmentalized gray and white matter of S1-S3 segments, proved to be highly variable for both post-constriction periods., J. Maršala, J. Kafka, N. Lukáčová, D. Čížková, M. Maršala, N. Katsube., and Obsahuje bibliografii
The CD8+ natural killer (NK) subpopulation has recently been identified as a fast and reliable biodosimetric indicator within human peripheral blood mononuclear cells (PBMC) in vitro. In irradiated and subsequently cultivated PBMC, a decrease of the relative number of intact CD3-CD8+ lymphocytes 16 and 48 h after treatment has allowed for estimating the received dose in the range of 0 - 10 Gy and lethal/sublethal dose discrimination, respectively. Here we show that suitable biodosimeters can also be found in the peripheral blood B-cell compartment. Multiparameter flow cytometric analysis of irradiated and subsequently cultivated human PBMC revealed that both the CD27+ and CD21- B-cell subpopulations can be used as biodosimeters and the CD19+CD27+ lymphocytes have proved useful for retrospective determination of the received dose in the range of 0 - 6 Gy. In addition, several CD19+ lymphocyte subsets characterized by co-expression of CD21, CD27 and CD38 have been shown to bear biodosimetric potential, too. However, when important parameters like the original size within the CD19+ compartment, its radiation-induced changes and data variation had been taken into account, the CD27+ subpopulation proved superior to the other B-cell subpopulations and subsets. It appears that, in the dose range of 0 - 6 Gy, the relative decrease of CD27+ B lymphocytes provides more sensitive and reliable data than that of CD8+ NK-cells due mainly to lower data variation. In contrast to CD27+ B-cells, the proportions of CD27+ subpopulations of T-cells were not affected by irradiation. We have also proposed a simple experimental protocol based on full blood cultivation and three-color CD27/CD3/CD19 immuno-phenotyping as a time-saving and inexpensive approach for practical biodosimetric evaluations on simple, three-to-four color flow cytometers., Z. Řeháková, J. Šinkora, M. Vlková, D. Vokurková, J. Österreicher, J. Vávrová, D. Driák., and Obsahuje bibliografii a bibliografické odkazy
In the current study, we tested a hypothesis that CD36 fatty acid (FA) transporter might affect insulin sensitivity by indirect effects on FA composition of adipose tissue. We examined the effects of CD36 downregulation by RNA interference in 3T3-L1 adipocytes on FA transport and composition and on sensitivity to insulin action. Transfected 3T3-L1 adipocytes, without detectable CD36 protein, showed reduced neutral lipid levels and significant differences in FA composition when levels of essential FA and their metabolites were lower or could not be detected including gamma linolenic (C18:3 n6), eicosadienic (C20:2 n6), dihomo-gamma linolenic (C20:3 n6), eicosapentaenoic (EPA) (C20:5 n3), docosapentaenoic (DPA) (C22:5 n3), and docosahexaenoic (DHA) (C22:6 n3) FA. Transfected 3T3-L1 adipocytes exhibited a significantly higher n6/n3 FA ratio, reduced Δ5-desaturase and higher Δ9-desaturase activities. These lipid profiles were associated with a significantly reduced insulin-stimulated glucose uptake (4.02±0.1 vs. 8.42±0.26 pmol.10-3 cells, P=0.001). These findings provide evidence that CD36 regulates FA composition thereby affecting sensitivity to insulin action in 3T3-L1 adipocytes., K. Kontrová, J. Zídková, B. Bartoš, V. Skop, J. Sajdok, L. Kazdová, K. Mikulík, P. Mlejnek, V. Zídek, M. Pravenec., and Obsahuje bibliografii a bibliografické odkazy
Cell-penetrating compounds are substances that enhance the cellular uptake of various molecular cargoes that do not easily cross the cellular membrane. The majority of cell-penetrating compounds described in the literature are cell-penetrating peptides (CPPs). This review summarizes the various structural types of cell-penetrating compounds, with the main focus on CPPs. The authors present a brief overview of the history of CPPs, discuss the various types of conjugation of CPPs to biologically active cargoes intended for cell internalization, examine the cell-entry mechanisms of CPPs, and report on the applications of CPPs in research and in preclinical and clinical studies., E. Böhmová, D. Machová, M. Pechar, R. Pola, K. Venclíková, O. Janoušková, T. Etrych., and Obsahuje bibliografii
Summary The aim of this study was to characterize an in vitro modulating effect of three commensal Lactobacillus strains on cellular differentiation of non-transformed crypt-like rat small intestinal cell line IEC-18. IEC-18 was grown on extracellular matrix, with or without presence of Lactobacillus strains. Gene expression of IEC-18 bacterial detection system - such as Toll-like receptors TLR-2, TLR-4, signal adapter MyD88, cytoplasmic NOD2 receptor, inflammatory cytokines IL-18, IL-1β, chemokine IL-8 and enzyme caspase-1 - was evaluated using real-time PCR. Expression and localization of TLR-2, TLR-4, IL-18 and caspase-1 proteins was demonstrated by Western blotting and immunofluorescent staining. Secretion of IL-18 to apical and basolateral surfaces was assayed by ELISA. Our results suggested that L. casei LOCK0919 accelerated differentiation of IEC-18 by stimulating TLR-2, TLR-4, MyD88, IL-18, caspase-1 mRNAs and proteins. L. casei LOCK0919 increased expression and transfer of villin and β-catenin from cytoplasm to cell membrane. Presence of L. rhamnosus LOCK0900 resulted in detachment of IEC-18 layer from extracellular matrix leading to induction of IL-1β, of TLR-2 and IL-8 mRNAs and stimulation of MyD88, caspase-1 and cytosolic receptor NOD2 mRNAs. L. rhamnosus LOCK0908 was not recognized by TLR-2 or TLR-4 receptors. Lactobacilli-IEC-18 crosstalk enhanced immune and barrier mucosal functions., J. Kolínská, M. Zákostelecká, Z. Zemanová, V. Lisa, J. Goliáš, H. Kozáková, B. Dvořák., and Seznam literatury
The aim of this study was to compare the central and peripheral components of cardiorespiratory fitness during incremental to maximal exercise between older men who were either recreational athletes (RA) or leisurely active (LA) men, i.e., those who fall between trained and untrained. This was a crosssectional study in which all subjects completed an exercise test on a cycle ergometer. Maximal oxygen consumption (VO2max) and ventilatory threshold (VT) were assessed using gas analysis, and central components of VO2max were assessed using a non-invasive thoracic bio-impedance device. VO2max (RA: 45.1±4.8 ml/kg/min; LA: 32.2±4.6 ml/kg/min, p≤0.001) and SV at maximal exercise (RA: 133.5±24.96 ml/beat; LA: 107.9±17.6 ml/beat, p=0.005) were higher in the RA group compared to the LA group. A plateau in SV occurred between 30-45 % of maximal exercise capacity in the RA group. No differences in SV were observed across workloads in the LA group. No differences in the calculated arterio-venous oxygen difference ((a-v)O2diff) were observed between groups. In conclusions, training volume appears to influence central components of cardiorespiratory fitness among a matched sample of older men who are neither trained nor untrained. This builds a case for increasing the volume of training to preserve cardiorespiratory fitness among older men., C. D. O'neill, D. S. Kimmerly, S. Dogra., and Obsahuje bibliografii
As a consequence of enhanced production of oxygen free radicals, lipid peroxidation leads to the degradation of membrane lipids and disturbances of membrane permeability. Lipid peroxidation increases under stress conditions such as hypoxia, ischemia or acidosis as well as in metabolic diseases, e.g. diabetes mellitus. We have shown that subcomatous doses of insulin (6.0 IU/kg) significantly increase thiobarbituric acid reactive substances (TBARs), especially malondialdehyde (MDA) - the endproduct of lipid peroxidation, in the brain and heart of mice. In our model of insulin-induced hypoglycemia, mice were treated with the neuroprotective, peptide-containing drug Cerebrolysin (100 mg/kg b.w.). Animals were sacrificed by decapitation two or three hours after the injection of tested substance and samples were taken to determine several serum parameters (glucose, total protein, triglycerides and lactic acid) and TBARs in the brain and heart. Although Cerebrolysin was not able to affect serum parameters after subcomatous insulin injection, the drug significantly influenced lipid peroxidation. A single injection of Cerebrolysin already decreased TBARs levels in the brain and heart tissue. Presuming that an increase of TBARs reflects disturbances of the cell membrane, we have documented a promising effect of Cerebrolysin on cell integrity., J. Patočková, M. Kršiak, P. Marhol, E. Tůmová., and Obsahuje bibliografii
Short-term weight-reducing regimens were shown to influence fatty acid composition of serum lipids unfavorably. Adding long chain n-3 polyunsaturated fatty acids (n-3 LC PUFA) to a low-calorie diet (LCD) could avoid these changes. The aim of this study was to examine the effect of a short-term in-patient weight-reducing regimen including LCD with yogurt enriched by low doses of n-3 PUFA (n-3 LCD). The enriched yogurt contained 790 mg of fish oil, predominantly eicosapentaenoic (20:5n-3; EPA) and docosahexaenoic (22:6n-3; DHA). Forty obese women were randomly assigned to the group consuming LCD and joghurt either with or without n-3 enrichment. Following the 3-week diet in the n-3 LCD group a significantly higher increase in the proportion of n-3 LC PUFA (sum of n-3 FA, EPA and DHA) in serum lipids was confirmed. In phospholipids (PL) a significant difference in the sum of n-6 fatty acids was found, a decrease in the n-3 LCD group and an increase in LCD group. Significantly higher increase in the PL palmitate (16:0) was shown in the LCD group. The results suggest that low doses of n-3 fatty acid enrichment can help to avoid unfavorable changes in fatty acid composition in serum lipids after a short-term weight-reducing regimen., P. Hlavatý, M. Kunešová, M. Gojová, E. Tvrzická, M. Vecka, P. Roubal, M. Hill, K. Hlavatá, P. Kalousková, V. Hainer, A. Žák, J. Drbohlav., and Obsahuje bibliografii a bibliografické odkazy
Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of heart failure (HF). Our aim was to determine the activities of circulating MMP-2 and MMP-9 in patients with HF in respect of gender, comorbidities and treatment (n=51). We did not reveal any differences in circulating pro-MMP-2 and pro-MMP-9 activities between the patients with HF and without it. However, there was a decrease in activity of pro-MMP-2 in treated hypertensive participants versus healthy ones. In contrast, we observed increased pro-MMP-2 activity in hypertensive participants with coexistent HF versus hypertensive participants without HF. In addition, a decrease in pro-MMP-2 activity was shown in women suffering from HF versus men suffering from HF. In conclusion, potential inhibitory effect of antihypertensive treatment on pro-MMP-2 activity was found. Coexistent HF with hypertension probably reduces the inhibitory effect of antihypertensive treatment on pro-MMP-2 activity. Our data also suggest the role of potential cardioprotective factors influencing the activity of pro-MMP-2 in women., E. Giannakos, E. Vardali, M. Bartekova, M. Fogarassyova, M. Barancik, J. Radosinska., and Obsahuje bibliografii