Reactive hyperemia (RH) in forearm muscle or skin microcirculation has been considered as a surrogate endpoint in clinical studies of cardiovascular disea e. We evaluated two potential confounders that might limit such use of RH, namely laterality of measurement and intake of non-steroidal anti-inflammatory drugs (NSAIDS). Twenty-three young non-smoking healthy adults were enrolled. In Experiment 1 (n=16), the RH elicited by 3 min of ischemia was recorded in the muscle (strain gauge plethysmography, hand excluded) and skin (laser Doppler imaging) of both forearms. In Experiment 2 (n=7), RH was determined in the dominant forearm only, one hour following oral acetylsalicylic acid (1 g) or placebo. In Experiment 1, peak RH was identical in both forearms, and so were the corresponding durations of responses. RH lasted significantly less in muscle than in skin (p=0.003), a hitherto unrecognized fact. In the skin, acetylsalicylate reduced duration (43 vs. 57.4 s for placebo, p=0.03), without affecting the peak response. In muscle, duration tended to decrease with acetylsalicylate (21.4 vs. 26.0 s with placebo, p=0.06) and the peak increase in blood flow was blunted (27.2 vs. 32.4 ml/min/100 ml tissue with placebo, p=0.003). We conclude that, when using RH as a surrogate endpoint in studies of cardiovascular disease, a confounding by laterality of measurement need not be feared, but NSAIDS may have an influence, although perhaps not on the peak response in the skin., G. Addor, A. Delachaux, B. Dischl, D. Hayoz, L. Liaudet, B. Waeber, F. Feihl., and Obsahuje bibliografii a bibliografické odkazy
Bone remodeling is a tightly coupled process consisting of repetitive cycles of bone resorption and formation. Both processes are governed by mechanical signals, which operate in conjunction with local and systemic factors in a discrete anatomic structure designated a basic multicellular unit (BMU). The microenvironment around total joint arthroplasty is a dynamic and complex milieu influenced by the chemical and physical stimuli associated with servicing the prosthesis. A key factor limiting the longevity of the prosthesis is polyethylene wear, which induces particle disease, and this may lead to increased and prolonged activity of BMUs resulting in periprosthetic osteolysis. Several pathways regulating BMU function have been reported in the past, including RANKL/RANK/OPG/TRAF6, TNF-α/TNFR/TRAF1, and IL-6/CD126/JAK/STAT. Moreover, the expression and functional activity of all these molecules can be affected by variations in their genes. These may explain the differences in severity of bone defects or prosthetic failure between patients with similar wear rates and the same prosthesis. Simultaneously, this data strongly support the theory of individual susceptibility to prosthetic failure., J. Gallo, M. Raška, F. Mrázek, M. Petřek., and Obsahuje bibliografii a bibliografické odkazy
Mechanism responsible for the en largement of end-expiratory lung volume (EELV) induced by chronic hypoxia remains unclear. The fact that the increase in EELV persists after return to normoxia suggests involvement of morphological changes. Because hypoxia has been also show n to activate lung mast cells, we speculated that th ey could play in the mechanism increasing EELV similar role as in vessel remodeling in hypoxic pulmonary hypertension (HPH). We, therefore, tested an effect of mast cells degranulation blocker disodium cromoglycate (DSCG) on hypoxia induced EELV enlargement. Vent ilatory parameters, EELV and right to left heart weight ratio (RV/LV+S) were measured in male Wistar rats. The experimental group (H+DSCG) was exposed to 3 weeks of normobaric hypoxia and treated with DSCG during the first four days of hypoxia, control group was exposed to hypoxia only (H), two others were kept in normoxia as non-treated (N) and treated (N+DSCG) groups. DSCG treatment significantly attenuated the EELV enlargement (H+DSCG=6.1 ± 0.8; H=9.2 ± 0.9; ml ± SE) together with the increase in minute ventilation (H+DSCG=190 ± 8; H=273 ± 10; ml/min ± SE) and RV/LV+S (H+DSCG=0.39 ± 0.03; H=0.50 ± 0.06)., H. Maxová, A. Hezinová, M. Vízek., and Obsahuje bibliografii a bibliografické odkazy
Hepcidin is a key regulator of iron homeostasis, while hemojuvelin is an important component of the hepcidin regulation pathway. It has been recently proposed that soluble hemojuvelin, produced from hemojuvelin by the protease furin, decreases hepcidin expression. The aim of the presented study was to examine the downregulation of hepcidin by chronic bleeding in hemojuvelin-mutant mice. Male mice with targeted disruption of the hemojuvelin gene (Hjv-/- mice) and wild-type littermates were maintained on an iron-deficient diet and subjected to weekly phlebotomies for 7 weeks. Gene expression was examined by real-time PCR. In wild type mice, repeated bleeding decreased hepcidin mRNA by two orders of magnitude. In Hjv-/- mice, basal hepcidin expression was low; however, repeated bleeding also decreased hepcidin mRNA content by an order of magnitude. Phlebotomies reduced hepatic iron overload in Hjv-/- mice by 80 %. Liver and muscle furin mRNA content was not significantly changed. No effect on hepatic Tmprss6 mRNA content was observed. Results from the study indicate that soluble hemojuvelin is not the sole factor responsible for hepcidin downregulation. In addition, the presented data suggest that, under in vivo conditions, tissue hypoxia does not transcriptionally regulate the activity of furin or TMPRSS6 proteases., J. Krijt ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Using high-resolution oxygraphy, we tested the changes of various parameters characterizing the mitochondrial energy provision system that were induced by peroxidative damage. In the presence of succinate as respiratory substrate, 3 mM t-butyl hydroperoxide increased respiration in the absence of ADP, which indicated partial uncoupling of oxidative phosphorylation. Low activity of coupled respiration was still maintained as indicated by the ADP-activated and oligomycin-inhibited respiration. However, during the incubation the phosphorylative capacity decreased as indicated by the continuous decrease of the mitochondrial membrane potential. Under these experimental conditions the maximum capacity of the succinate oxidase system was inhibited by 50 % in comparison with values obtained in the absence of t-butyl hydroperoxide. Our data thus indicate that the oxygraphic evaluation of mitochondrial function represents a useful tool for evaluation of changes participating in peroxidative damage of cell energy metabolism., P. Křiváková, A. Lábajová, Z. Červinková, Z. Drahota., and Obsahuje bibliografii a bibliografické odkazy
Hematopoiesis-modulating action of meloxicam, a cyclooxygenase-2 inhibitor, has been evaluated in mice. Increased serum level of granulocyte colony-stimulating factor (G-CSF) after meloxicam administration has been found in sublethally γ-irradiated animals. In further experiments hematopoiesis-stimulating effects of meloxicam and G-CSF given alone or in combination have been investigated. Granulocyte/macrophage progenitor cells counts were used to monitor these effects. Meloxicam and exogenous G-CSF did not act synergistically when given in combination, but could be mutually substituted during their repeated administration. The results suggest a promising possibility of using meloxicam as an auxiliary drug reducing the high costs of G-CSF therapy of myelosuppression., M. Hofer, M. Pospíšil, V. Znojil, J. Holá, A. Vacek, D. Štreitová., and Obsahuje bibliografii a bibliografické odkazy
The kidney is a common “victim organ” of various insults in critically ill patients. Sepsis and septic shock are the dominant causes of acute kidney injury, accounting for nearly 50 % of episodes of acute renal failure. Despite our substantial progress in the understanding of mechanisms involved in septic acute kidney injury there is still a huge pool of questions preclusive of the development of effective ther apeutic strategies. This review briefly summarizes our current knowledge of pathophysiological mechanisms of septic acute kidney injury focusing on hemodynamic alterations, peritubular dysfunction, role of inflammatory mediators and nitric oxide, mitochondrial dysfunction and structural chan ges. Role of proteomics, new promising laboratory method, is mentioned., J. Chvojka, R. Sýkora, T. Karvunidis, J. Raděj, A. Kroužecký, I. Novák, M. Matějovič., and Obsahuje bibliografii
The pathophysiology of microcirculation is intensively investigated to understand disease development at the microscopic level. Orthogonal polarization spectral (OPS) imaging and its successor sidestream dark-field (SDF) imaging are relatively new noninvasive optical techniques allowing direct visualization of microcirculation in both clinical and experimental studies. The goal of this experimental study was to describe basic microcirculatory parameters of skeletal muscle and ileal serous surface microcirculation in the rat using SDF imaging and to standardize the technical aspects of the protocol. Interindividual variability in functional capillary density (FCD) and small vessels (<25 μm in diameter) proportion was determined in anesthetized rats on the surface of quadriceps femoris (m. rectus femoris and m. vastus medialis) and serous surface of ileum. Special custom made flexible arm was used to fix the SDF probe minimizing the pressure movement artifacts. Clear high contrast images were analyzed off-line. The mean FCD obtained from the surface of skeletal muscle and ileal serous surface was 219 (213-225 cm/cm2) and 290 (282-298 cm/cm2) respectively. There was no statistically significant difference between rats in mean values of FCD obtained from the muscle (P = 0.273) in contrast to ileal serous surface, where such difference was statistically significant (P = 0.036). No statistically significant differences in small vessels percentage was detected on either the muscle surface (P = 0.739) or on ileal serous surface (P = 0.659). Our study has shown that interindividual variability of basic microcirculatory parameters in rat skeletal muscle and ileum is acceptable when using SDF imaging technique according to a highly standardized protocol and with appropriate fixation device. SDF imaging represents promising technology for experimental and clinical studies., Z. Turek, V. Černý, R. Pařízková., and Obsahuje bibliografii a bibliografické odkazy
Plasma procalcitonin (PCT) is a highly specific marker for the diagnosis of bacterial infections and sepsis. PCT levels are usually low in viral infections, chronic inflammation or postsurgical states. The purpose of this study was to characterize PCT plasma levels in patients with various types of ileus at preoperative stage, where the other inducing factors suchas a surgical stress are excluded. The prospective study was performed on 54 patients admitted to in-patient surgical department with a proven diagnosis of ileus. Patients were divided to three groups – obstructive, vascular and paralytic ileus. Plasma levels of PCT (Kryptor analysis), TNFα, IL-1β, IL-6, cortisol (ELISA) and CRP (Kryptor ultrasensitive analysis) were estimated before any invasive procedure was realized. We demonstrated significant elevation of PCT in both obstructive ileus in adhesions and vascular ileus compared with healthy subjects (p<0.01). PCT levels were not elevated in paralytic ileus. The regression coefficient was the highest for PCT and CRP (r=0.78, p<0.01), for TNFα and IL-8 (r=0.76, p<0.01) in vascular ileus. There was no significant correlation between PCT and other inflammatory parameters. The different types of ileus induce an elevation of plasma PCT levels and PCT shows itself as an acute phase reactant. The highest PCT concentrations were presented in patients with vascular ileus, whereas paralytic ileus revealed similar cytokine and PCT pattern as in healthy subjects. Plasma PCT estimation extended to a measurement of CRP and IL-6 may become a useful complementary examination for diagnostics of acute abdomen in patients., P. Maruna, R. Fraško, R. Gürlich., and Obsahuje bibliografii a bibliografické odkazy
Arterial wall stiffness is considered an independent cardiovascular risk factor. Aim of this study was to evaluate relationship between clinical, 24-hour, average day-time and night-time blood pressure (BP) and measures of arterial stiffness assessed by pulse wave velocity (PWV) (using SphygmoCor applanation tonometer) in essential hypertension (severe-resistant (RH, n=29) and moderate hypertension (EH, n=35)) and in normotensive control subjects (n-29) (NCS) matched by age. After multiple regression analysis, PWV remains significantly correlated mainly with night-time pulse pressure and to a lesser extent with age. PWV was significantly higher in RH compared to moderate EH and NCS., J. Rosa, B. Štrauch, O. Petrák, T. Pikus, R. Holaj, T. Zelinka, D. Wichterle, J. Widimský Jr., and Obsahuje bibliografii a bibliografické odkazy