An increase in the renal resistive index (RRI) in patients with essential hypertension (EH) predicts deterioration in renal function. In patients with EH, changes in hemodynamic parameters significantly affect the RRI. This study aimed to define changes in Ambulatory Blood Pressure Monitoring (ABPM) parameters that are significantly associated with a change in RRI in patients with EH. We evaluated ABPM and the RRI in 96 patients with EH without organ extrarenal changes at baseline and after two years of follow-up. The relationships between changes in ABPM parameters and the RRI over the period were evaluated. After two years of follow-up, the increase in RRI was consequential. Simultaneously, 24-h systolic blood pressure increased significantly and 24-h diastolic blood pressure decreased. In the whole group and in the group with calculated cystatin C clearance (eGFRcyst) ≥90 ml/min/1.73 m2 , the change in RRI significantly negatively correlated with the change in the ratio of 24-h diastolic to systolic blood pressure (D/S ratio), but also with the change in 24-h pulse blood pressure. However, in patients with eGFRcyst˂90 ml/min/1.73 m2 , only the change in the 24-h D/S ratio significantly correlated with the change in RRI. Based on the backward stepwise regression analysis, the change in RRI was significantly dependent only on the change in 24-h D/S ratio and not on the change in 24-h pulse pressure. A change in the ratio of diastolic to systolic pressure better reflects a change in RRI than a change in pulse pressure.
We honor here Hartmut Karl Lichtenthaler, a pioneer of plant physiology, plant biochemistry, plant biophysics, plant molecular biology, and stress physiology. His contributions to the ingenious use of chlorophyll a fluorescence imaging in understanding the physiological processes in leaves stand out. We wish him many happy and productive years of research and educating others., G. Govindjee., and Obsahuje bibliografické odkazy
An evaluation of possible interactions with enzymes of drug metabolism (cytochromes P450, CYP) is an important part of studies on safety and, in general, on the properties of any drug or biologically active compound. The article is focused on the preliminary metabolic study of selected 2,6,9-trisubstituted purine kinase inhibitors with significant anticancer activities which we have developed. The compounds BP-21 and BP-117 represent strong CDK inhibitors and the compound BPA-302 was developed as selective FLT3-ITD kinase inhibitor. Here, emphasis is placed on interactions of these compounds with the nine most important forms of CYP to evaluate the possibility of inhibition of these enzymes. The possibility of their inhibitory effect was studied in vitro on selected human liver microsomal CYP enzymes. The most affected enzyme was CYP2C19. Its activity dropped to 22 % of its original value by BPA-302, to 13 % by BP-21 and to 6 % by BP-117 at the highest concentration tested (250 µmol·l-1 ). The results suggest that the metabolism of concomitantly administered drugs should not be significantly affected at lower doses. Molecular docking of BPA-302 indicated that it can bind to active site of both CYP2C19 and CYP2D6 enzymes above the heme cofactor corroborating the experimental data.
Nickel is a ubiquitous environmental pollutant, which has various effects on reproductive endocrinology. In this study, human adrenocortical carcinoma (NCI-H295R) cell line was used as an in vitro biological model to study the effect of nickel chloride (NiCl2) on the viability and steroidogenesis. The cells were exposed to different concentrations (3.90; 7.80; 15.60; 31.20; 62.50; 125; 250 and 500 μM) of NiCl2 and compared with control group (culture medium without NiCl2). The cell viability was measured by the metabolic activity assay. Production of sexual steroid hormones was quantified by enzyme linked immunosorbent assay. Following 48 h culture of the cells in the presence of NiCl2 a dose-dependent depletion of progesterone release was observed even at the lower concentrations. In fact, lower levels of progesterone were detected in groups with higher doses (≥125 μM) of NiCl2 (P<0.01), which also elicited cytotoxic action. A more prominent decrease in testosterone production (P<0.01) was also noted in comparison to that of progesterone. On the other hand, the release of 17β-estradiol was substantially increased at low concentrations (3.90 to 62.50 μM) of NiCl2. The cell viability remained relatively unaltered up to 125 μM (P>0.05) and slightly decreased from 250 μM of NiCl2 (P<0.05). Our results indicate endocrine disruptive effect of NiCl2 on the release of progesterone and testosterone in the NCI-H295R cell line. Although no detrimental effect of NiCl2 (≤62.50 μM) could be found on 17β-estradiol production, its toxicity may reflect at other points of the steroidogenic pathway., Norbert Lukac, Zsolt Forgacs, Hana Duranova, Tomas Jambor, Jirina Zemanova, Peter Massanyi, Barbara Tombarkiewicz, Shubhadeep Roychoudhury, Zuzana Knazicka., and Obsahuje bibliografii
In order to clear airways and lungs defensive reflexes are
provoked rather by the dynamic phase of mechanical stimulus. It
is speculated that provocation of defensive response depends not
only on stimulus duration but also on stimulus velocity. Fourteen
adult rabbits were anaesthetized and tracheotomized. Mechanical
stimulus was provoked by a mechanical probe introduced
through the tracheotomy and rotated by a small electrical motor
using a rotational velocity of 40 rpm/s and 20 rpm/s. Threshold,
incidence and intensity of cough reflex (CR) were analyzed for
each animal. Statistical comparisons between two velocities were
performed using Friedman nonparametric test for repeated
measurements. Results are median (25-75 %). The threshold of
CR was significantly increased (p=0.005) from 350 ms (300-500
ms) to 550 ms (350-1150 ms) and the incidence of cough reflex
was significantly reduced (p=0.002) from 50 % (19-50 %) to
0 % (0-25 %) when the rotational velocity of the mechanical
probe was reduced by half. The findings of this study are of
interest as they show that protective reflex cough, an important
mechanism that allows clearing airways even during sleep or
anesthesia, is tuned by mechanical stimulus velocity.
Parasitic organisms inhabiting the alimentary canal should permanently resist the destructive action of host digestive enzymes. The intestinal parasites were shown to produce specific protease inhibitors protecting them from proteolysis. However, little is known about this adaptive mechanism in cestodes so far, especially for the tapeworms dwelling inside the fish intestines. Here, we explored the ability to inactivate proteolytic enzymes in the fish tapeworm Eubothrium rugosum (Batsch, 1786) (Bothriocephalidea) parasitising the intestine of wild burbot, Lota lota (Linnaeus). The assays were conducted with different concentrations of commercial trypsin and homogenate of intestinal mucosa both being the sources of proteinases. The incubation of live E. rugosum in trypsin solutions of two different concentrations caused a significant decrease in the enzyme activity. The extent of activity reduction was dependent on trypsin concentration. At the same time, the inhibitory effect of the worm incubation medium turned out to be statistically insignificant. These findings suggest partial adsorption of the enzyme to the tegument surface, with its further inactivation. In contrast to the incubation medium, the worm extract suppressed over 80% of trypsin activity and nearly half of the proteolytic activity in the mucosa homogenate. Notably, the inhibitory activity of the tapeworms hardly depended on their size characteristics. Finally, the research has demonstrated secretion of proteinase inhibitor in E. rugosum, which appears to be essential for its survival in enzymatically hostile environment., Galina I. Izvekova, Tatyana V. Frolova, Evgeny I. Izvekov., and Obsahuje bibliografii
This paper investigates the incipient motion of sediment particles under non-uniform flow in river and laboratory. In rivers, the non-uniform flow is often observed due to the presence of various bed forms. Threshold condition has been examined by using the Shields diagram based on the uniform flow assumption, however, this approach can be led to fallacious results for non-uniform flows where the effect of pressure gradient is significant due to bed forms. This study investigates the chronological order of incipient motion of the particles, the average threshold velocity (Ucr), and Shields parameter for non-uniform flows. River data collection with gravel is used for investigating the incipient motion of surface layer of river bed and the laboratory data collection is considered studying the incipient motion of sub-surface layer of river. Both river and laboratory data collections are conducted in the presence of bed forms. Results reveal that the Shields diagram underestimates the particle incipient motion under accelerating and decelerating flows for the both case of laboratory and river. In both weak and general motion in the laboratory, the values of the critical Shields parameter are located below the Shields diagram, showing no particle motion. Our analysis shows that the incipient motion in river is affected by the presence of bed forms, river width changes, and flow non-uniformity conditions. The results show that in the accelerating flow (the bed form exit with a negative slope), the incipient motion is greater than the decelerating flow (the bed form entrance with a positive slope).
Chronic inflammation of adipose tissue is associated with the pathogenesis of cardiovascular diseases. Mast cells represent an important component of the innate defense system of the organism. In our work, we quantified mast cell number in epicardial adipose tissue (EAT), subcutaneous adipose tissue (SAT), and right atrial myocardium (RA) in patients undergoing open heart surgery (n=57). Bioptic samples of EAT (n=44), SAT (n=42) and RA (n=17) were fixed by 4 % paraformaldehyde and embedded into paraffin. An anti-mast cell tryptase antibody was used for immunohistochemical detection and quantification of mast cells. We also demonstrated immunohistochemically the expression of CD117 and chymase markers. In EAT of patients with coronary artery disease (CAD), higher incidence of mast cells has been found compared to patients without CAD (3.7±2.6 vs. 2.1±1.2 cells/mm2 ). In SAT and RA, there was no difference in the number of mast cells in CAD and non-CAD patients. Mast cells in SAT, EAT and RA expressed CD117 and chymase. An increased incidence of mast cells in EAT of CAD patients may indicate the specific role of these inflammatory cells in relation to EAT and coronary arteries affected by atherosclerosis., Karolína Rozsívalová, Aneta Pierzynová, Helena Kratochvílová, Jaroslav Lindner, Michal Lipš, Tomáš Kotulák, Peter Ivák, Ivan Netuka, Martin Haluzík, Tomáš Kučera., and Obsahuje bibliografii
The biology of sialic acids has been an object of interest in many models of acquired and inherited skeletal muscle pathology. The present study focuses on the sialylation changes in mouse skeletal muscle after invasion by the parasitic nematode Trichinella spiralis (Owen, 1835). Asynchronous infection with T. spiralis was induced in mice that were sacrificed at different time points of the muscle phase of the disease. The amounts of free sialic acid, sialylated glycoproteins and total sialyltransferase activity were quantified. Histochemistry with lectins specific for sialic acid was performed in order to localise distribution of sialylated glycoconjugates and to clarify the type of linkage of the sialic acid residues on the carbohydrate chains. Elevated intracellular accumulation of α-2,3- and α-2,6-sialylated glycoconjugates was found only within the affected sarcoplasm of muscle fibres invaded by the parasite. The levels of free and protein-bound sialic acid were increased and the total sialyltransferase activity was also elevated in the skeletal muscle tissue of animals with trichinellosis. We suggest that the biological significance of this phenomenon might be associated with securing integrity of the newly formed nurse cell within the surrounding healthy skeletal muscle tissue. The increased sialylation might inhibit the affected muscle cell contractility through decreased membrane ion gating, helping the parasite accommodation process., Rositsa Milcheva, Dimitar Ivanov, Ivan Iliev, Russy Russev, Svetlozara Petkova, Pavel Babál., and Obsahuje bibliografii
Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is a technique used in patients with severe heart failure. The aim of this study was to evaluate its effects on left ventricular afterload and fluid accumulation in lungs with electrical impedance tomography (EIT). In eight swine, incremental increases of extracorporeal blood flow (EBF) were applied before and after the induction of ischemic heart failure. Hemodynamic parameters were continuously recorded and computational analysis of EIT was used to determine lung fluid accumulation. With an increase in EBF from 1 to 4 l/min in acute heart failure the associated increase of arterial pressure (raised by 44 %) was accompanied with significant decrease of electrical impedance of lung regions. Increasing EBF in healthy circulation did not cause lung impedance changes. Our findings indicate that in severe heart failure EIT may reflect fluid accumulation in lungs due to increasing EBF., Michaela Popková, Eduard Kuriščák, Pavel Hála, David Janák, Leoš Tejkl, Jan Bělohlávek, Petr Ošťádal, Petr Neužil, Otomar Kittnar, Mikuláš Mlček., and Obsahuje bibliografii