This review, which summarizes our findings concerning the long-term effects of pre-, peri- and postnatal factors affecting development, nociception and sensorimotor functions, focuses on three areas: 1) perinatal factors influencing nociception in adult rats were examined in rats with hippocampal lesions, after the administration of stress influencing and psychostimulant drugs (dexamethasone, indomethacine and methamphetamine); 2) the effect of pre- and early postnatal methamphetamine administration was shown to impair the development of sensorimotor functions tested in rat pups throughout the preweaning period; 3) the effect of extensive dorsal rhizotomy of the brachial plexus during the early postnatal period was studied with respect to neuropathic pain development and sensorimotor functions. The present study indicates that prenatal or neonatal stress, as well as various drugs, may disturb the development of the nociceptive system and cause long-term behavioral changes persisting to adulthood and that some types of neuropathic pain cannot be induced during the first two postnatal weeks at all. A mature nervous system is required for the development of the described pathological behaviors., R. Rokyta, A. Yamamotová, R. Šlamberová, M. Franěk, Š. Vaculín, L. Hrubá, B. Schutová, M. Pometlová., and Obsahuje bibliografii a bibliografické odkazy
In modern societies, living organisms are exposed daily to multiform pollution from industrial chemical products. Some of these substances have been shown to affect the endocrine system, and have been termed endocrine disruptors (EDs). Bisphenol A (BPA), which can leach from plastics, and parabens, used in cosmetic products, are among the most well-studied. Prenatal development is a vulnerable phase of human life, and disruptions during this period may have lifelong consequences. Since EDs are known to cross the placental barrier and BPA may accumulate in the fetus, "BPA-free" products have been introduced to the market. However, such products often contain alternative bisphenols (e.g. BPS, BPF) that have not yet been extensively examined or regulated. Moreover, alternative bisphenols often occur together with BPA. The human organism is thus exposed to a mixture of EDs, some of which can have additive or synergic effects. Recent findings have also shown that paraben exposure can alter bisphenol pharmacokinetics. Taking into account the widespread occurrence of various EDs and the potential multiplicity of their effects, doses of EDs currently considered safe may not actually be as safe as they appear, especially during pregnancy., L. Kolatorova, M. Duskova, J. Vitku, L. Starka., and Obsahuje bibliografii
Since close relationship was shown between drug addiction and memory formation, the aim of the present study was to investigate the effects of interaction between prenatal methamphetamine (MA) exposure and MA treatment in adulthood on spatial and non-spatial memory and on the structure of the N-methyl-D-aspartate (NMDA) receptors in the hippocampus. Adult male rats prenatally exposed to MA (5 mg/kg) or saline were tested in adulthood. Non-spatial memory was examined in the Object Recognition Test (ORT) and spatial memory in the Object Location Test (OLT) and in the Memory Retention Test (MRT) conducted in the Morris Water Maze (MWM), respectively. Based on the type of the memory test animals were injected either acutely (ORT, OLT) or long-term (MWM) with MA (1 mg/kg). After each testing, animals were sacrificed and brains were removed. The hippocampus was then examined in Western Blot analysis for occurrence of different NMDA receptors’ subtypes. Our results demonstrated that prenatal MA exposure affects the development of the NMDA receptors in the hippocampus that might correspond with improvement of spatial memory tested in adulthood in the MWM. On the other hand, the effect of prenatal MA exposure on nonspatial memory examined in the ORT was the opposite. In addition, we showed that the effect of MA administration in adulthood on NMDA receptors is influenced by prenatal MA exposure, which seems to correlate with the spatial memory examined in the OLT., R. Šlamberová, M. Vrajová, B. Schutová, M. Mertlová, E. Macúchová, K. Nohejlová, L. Hrubá, J. Puskarčíková, V. bubeníková-Valešová, A. Yamamotová., and Obsahuje bibliografii
Monodisperse macroporous poly(glycidyl methacrylate) (PGMA) microspheres were used as a template for preparing porous silica particles. The starting polymer microspheres that were 9.3 μm in size were synthesized by multistep swelling polymerization using a modified Ugelstad technique. Subsequently, silica (SiO2) was deposited on the surface and inside the PGMA microspheres to produce poly(glycidyl methacrylate)-silica hybrid particles (PGMA-SiO2). Upon calcination of the PGMA-SiO2 microspheres, porous silica particles were formed. The morphology, particle size, polydispersity and inner structure of the silica microspheres were investigated by scanning and transmission electron microscopy. Thermogravimetric analysis and dynamic adsorption of nitrogen determined the amount of silica formed and its specific surface area. Compared with the starting PGMA microspheres, the size of the porous silica particles decreased by up to 30%. These porous silica microspheres are promising for chromotography and biomedical applications., S. Grama, D. Horák., and Obsahuje bibliografii
Increasing hemodynamic load during early postnatal development leads to rapid growth of the left ventricular (LV) myocardium, which is associated with membrane phospholipid (PL) remodeling characterized by n-3 polyunsaturated fatty acids (PUFA) accumulation. The aim of this study was to examine the influence of additional workload imposed early after birth when ventricular myocytes are still able to proliferate. Male Wistar rats were subjected to abdominal aortic constriction (AC) at postnatal day 2. Concentrations of PL and their fatty acid (FA) profiles in the LV were analyzed in AC, sham-operated (SO) and intact animals on postnatal days 2 (intact only), 5 and 10. AC resulted in LV enlargement by 22 % and 67 % at days 5 and 10, respectively, compared with age-matched SO littermates. Concentrations of phosphatidylcholine, cardiolipin, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine and sphingomyelin decreased in AC myocardium, albeit with different time course and extent. The main effect of AC on FA remodeling consisted in the accumulation of n-3 PUFA in PL. The most striking effect of AC on FA composition was observed in phosphatidylinositol and cardiolipin. We conclude that excess workload imposed by AC inhibited the normal postnatal increase of PL concentration while further potentiating the accumulation of n-3 PUFA as an adaptive response of the developing myocardium to accelerated growth., F. Novák, ... [et al.]., and Obsahuje seznam literatury
We investigated non-invasively cardiac contractility and autonomic nervous activity during presyncopal orthostatic stress induced in healthy humans. A graded orthostatic stress (GOS) paradigm, consisting of head-up tilt (HUT) combined with lower body negative pressure (LBNP) of increasing magnitude, was used to reach a presyncopal end-point in 15 healthy adults. Continuous beat-to-beat hemodynamic and autonomic parameters were recorded. From supine control (C1) to presyncope (PS), total peripheral resistance index (TPRI) decreased from 2300±500 to 1910±320 dyne*s*m²/cm^5 (p=0.004), index of contractility (IC) from 59±14 to 27±6 1000/s (p<0.0001), left ventricular working index (LVWI) from 5.2±1.3 vs. 3.6±0.6 mmHg*L/(min*m²) (p=0.0001) and acceleration index (ACI) from 65±18 vs. 54±15 100/s² (p=0.04). Low frequency variation of diastolic blood pressure (LFnudBP) increased from 51±14 to 67±11 % (p=0.0006) and of systolic blood pressure (LFnusBP) from 50±6 vs. 67±8 % (p<0.0001). High frequency variation of RR-interval (HFms²RRI) decreased from 385±320 to 38±43 ms² (p=0.001). From late GOS (G3) to PS, TPRI decreased from 2540±640 to 1910±320 dyne*s*m²/cm^5 (p=0.003), IC from 35±6 to 27±6 1000/s (p=0.003), LVWI from 4.6±0.9 to 3.6±0.6 mmHg*L/(min/m²) (p=0.003), LFnusBP from 71±8 to 67±8 % (p=0.03), LFmmHg²dBP from 6.6±4.0 to 4.8±2.9 mmHg² (p=0.0001), LFmmHg²sBP from 9.7±7.8 to 7.4±4.8 mmHg² (p=0.01). HFnuRRI increased from 19±8 to 28±13 % (p=0.008). Myocardial contractility indices and parameters of sympathetic activity were reduced in the presyncopal state, while parasympathic activity was increased. This suggests a decrease in cardiac contractility during orthostatically induced presyncope in healthy subjects., E. K. Grasser, N. Goswami, H. Hinghofer-Szalkay., and Obsahuje seznam literatury
Negative expiratory pressure (NEP) applied at the mouth during tidal expiration provides a non-invasive method for detecting expiratory flow limitation. Forty-two children were studied, i.e. 25 children with different respiratory symptoms (R) and 17 without any respiratory symptoms (NR). Children were examined without any sedation. A preset NEP of -5 cm H 2 O was applied; its duration did not exceed duration of tidal expiration. A significance of FL was judged by determining of a flow-limited range (in % of tidal volume). FL was found in 48 % children of R group. No patient of the NR group elicited FL (P<0.001 R vs. NR). The frequency of upper airway collapses was higher in R group (12 children) than in NR gr oup (5 children). In conclusion, a high frequency of tidal FL in the R group was found, while it was not present in NR group. A relatively high frequency of expiratory upper airway collapses was found in both groups, but it did not differ significantly. NEP method represents a reasonable approach for tidal flow limitation testing in non-sedated preschool children., A. Jiřičková, J. Šulc, P. Pohunek, O. Kittnar, A. Dohnalová, J Kofránek., and Obsahuje bibliografii
a1_Antiphospholipid antibodies (APAs) are characterized as a heterogeneous population of autoantibodies directed against different target antigens, predominantly anionic phospholipids or phospholipid-containing structures. The presence of APAs has been strongly associated with a variety of clinical disorders including adverse pregnancy complications such as spontaneous abortions, pregnancy-induced hypertension, preeclampsia and intrauterine growth retardation. The purpose of this study was to compare the prevalence of anticardiolipin antibodies (ACAs), which are routinely examined, with APAs directed against phosphatidylserine (APS), phosphatidylinositol (API), phosphatidylethanolamine (APE) and phosphatidylcholine (APC) in the sera of pregnant women. We examined 410 serum samples of pregnant women hospitalized in the department for pathological pregnancies. They underwent prenatal biochemical screening of fetal congenital abnormalities in the first and the second trimester of gravidity. Anticardiolipin IgG and IgM were measured using commercial ELISA kits (ImmuLisaTM Anti-Cardiolipin Antibody), whereas APS, APE, API and APC were determined by our modified ELISA kit. Among 410 pregnant women we found 21 patients (5.1 %) positive for ACA IgG (>20 GPL) and 30 patients (7.3 %) positive for ACA IgM (>10 MPL). It was found that 7.8 % of pregnant women had at least one high-titer APA IgG and 9.8 % high-titer APA IgM. One third of ACA IgG or IgM positive sera contained polyspecific autoantibodies reactive to at least two various phospholipids. In the group of IgG ACA positive women, 28.6 % patients were positive for APS, 28.6 % were positive or moderately positive for API, 23.8 % for APC and 19 % for APE. In the group of IgM ACA positive women, 33.3 % were also positive for APS, 26.7 % for APE, 26.7 % for API and 23.3 % for APC were present., a2_IgG and IgM ACA negative patients exhibited a significantly lower incidence of other APA than the group of ACA positive pregnant women. It still remains to clarify if the routine examination of APA reacting with other anionic and zwitterionic antigens other than cardiolipin would improve the probability of identifying women liable to adverse pregnancy complications., L. Fialová, L. Mikulíková, I. Matouš-Malbohan, O. Benešová, A. Zwinger., and Obsahuje bibliografii
Excessive production of oxygen free radicals has been regarded as a causative common denominator of many pathological processes in the animal kingdom. Hydroxyl and nitrosyl radicals represent the major cause of the destruction of biomolecules either by a direct reaction or by triggering a chain reaction of free radicals. Scavenging of free radicals may act preventively or therapeutically. A number of substances that preferentially react with free radicals can serve as scavengers, thus increasing the internal capacity/activity of endogenous antioxidants and protecting cells and tissues against oxidative damage. Molecular hydrogen (H2) reacts with strong oxidants, such as hydroxyl and nitrosyl radicals, in the cells, that enables utilization of its potential for preventive and therapeutic applications. H2 rapidly diffuses into tissues and cells without affecting metabolic redox reactions and signaling reactive species. H2 reduces oxidative stress also by regulating gene expression, and functions as an anti-inflammatory and anti-apoptotic agent. There is a growing body of evidence based on the results of animal experiments and clinical observations that H2 may represent an effective antioxidant for the prevention of oxidative stress-related diseases. Application of molecular hydrogen in situations with excessive production of free radicals, in particular, hydroxyl and nitrosyl radicals is relatively simple and effective, therefore, it deserves special attention., J. Slezák, B. Kura, K. Frimmel, M. Zálešák, T. Ravingerová, C. Viczenczová, Ľ. Okruhlicová, N. Tribulová., and Obsahuje bibliografii
Inflammatory changes, both in the arterial wall and adipose tissue, play a crucial role in the development of atherosclerosis. We measured the gene expression of tumor necrosis factor-alpha (TNFα), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6 (IL-6) in adipose tissue (AT) of living kidney donors (LKD) and patients with peripheral arterial disease (PAD). Quantitative polymerase chain reaction (qPCR) and flow cytometry analyses were performed in subcutaneous (SAT), visceral (VAT), and perivascular adipose tissue (PVAT). Data of PAD patients showed significantly higher expression in VAT in all three genes (TNFα 5-fold, p<0.05; MCP-1 3.6-fold, p<0.05; IL-6 18.8-fold, p<0.001). The differences in PVAT and SAT were less significant. Total body pro-inflammatory status was documented by higher TNFα concentration in patients (4.86± 1.4 pg/ml) compared to LKDs (2.14±0.9 pg/ml; p<0.001), as was hsCRP (11.8±7.0 in PAD; 1.5±0.48 in LKDs; p=0.017). We found no age-dependent relationship between gene expression vs. TNFα and hsCRP concentrations in both compared groups. No effect of the atherosclerosis score on gene expression and circulating inflammatory markers within the PAD group was observed. Our results suggest that the AT of PAD patients infiltrated with macrophages produces more cytokines involved in the development of inflammation and atherosclerosis., S. Čejková, I. Králová Lesná, J. Froněk, L. Janoušek, A. Králová, J. Ždychová, R. Poledne., and Obsahuje bibliografii