In this work, design and synthesis of high-molecular-weight N-(2- hydroxypropyl)methacrylamide-based polymer drug delivery systems tailored for cancer therapy is summarized. Moreover, the influence of their architecture on tumor accumulation and in vivo anti-cancer efficacy is discussed. Mainly, the high-molecularweight delivery systems, such as branched, grafted, multi-block, star-like or micellar systems, with molecular weights greater than the renal threshold are discussed and reviewed in detail., L. Kostka, T. Etrych., and Obsahuje bibliografii
Schizophrenia is a devastating disorder affecting 1 % of the world's population. An important role in the study of this disease is played by animal models. Since there is evidence that acute psychotic episodes can have consequences on later cognitive functioning, the present study has investigated the effects of a single systemic application of higher doses of (+)MK-801 (3 mg/kg and 5 mg/kg) to adult male Long-Evans rats from the Institute’s breeding colony on delayed testing in the active place avoidance task with reversal on the Carousel (a rotating arena). Besides significant mortality due to the injections, a disruption of procedural functions in active place avoidance, after the dose 5 mg/kg was observed. It was concluded that Long-Evans rats from our breeding colony do not represent a suitable biomodel for studying the effects of single high-dose NMDA antagonists., V. Lobellová, E. Brichtová, T. Petrásek, K. Valeš, A. Stuchlík., and Obsahuje bibliografii
We studied hsBAFF activity in in vitro mouse splenic B cells. hsBAFF effects on intracellular free Ca 2+ concentration ([Ca 2+ ] i ) were assayed, using a laser scanning confocal microscope with fluorescent probe, Fluo-3/AM. We showed that treatment of B cells with 0.5-5 μ g/ml hsBAFF resulted in significantly higher [Ca 2+ ] i levels in a dose-dependent fashion at 12 and 24 h, respectively (p<0.05 or p<0.01 vs. control). Furthermore, we noticed that 2.5 μ g/ml hsBAFF-treated cells were significantly resistant to decrease of cellular viability induced by thapsigargin (Tg), an endoplasmic reticulum (ER) Ca 2+ -ATPase inhibitor (p<0.05 hsBAFF plus Tg group vs. Tg group). Thus hsBAFF may promote B cell survival by direct upregulation of [Ca 2+ ] i physiological homeostasis contri buting to prevention of [Ca 2+ ] i dysfunction. Using immunocytochemistry and Western blot analysis, we found that the activation of ERK1/2 due to hsBAFF was triggered by a [Ca 2+ ] i -dependent pathway, leading to elevation of B cell proliferation. This is supported by the findings that intracellular Ca 2+ chelator BAPTA/AM attenuated phosphorylated ERK1/2 expression and cell proliferation in hsBAFF-stimulated B cells. hsBAFF-stimulated B cell proliferation was obviously reduced by mitogen extracellular kinase 1/2 (MEK1/2, upstream of ERK1/2) inhibitor U0126. Taken together, the main finding of this study is that hsBAFF elicits higher but homeostatic [Ca 2+ ] i levels, which regulates ERK1/2 activity and cell proliferation in in vitro B cells., J. Q. Liang, W. Zhang, L. Wen, W. Gao, S. Q. Zhang, L. Chen., and Obsahuje bibliografii
Chronic lung hypoxia results in hypoxic pulmonary hypertension. Concomitant chronic hypercapnia partly inhibits the effect of hypoxia on pulmonary vasculature. Adult male rats exposed to 3 weeks hypoxia (Fi02=0.1) combined with hypercapnia (FiC02=0.04-0.05) had lower pulmonary arterial blood pressure, increased weight of the right heart ventricle, and less pronounced structural remodeling of the peripheral pulmonary arteries compared with rats exposed only to chronic hypoxia (Fi02=0.1). According to our hypothesis, hypoxic pulmonary hypertension is triggered by hypoxic injury to the walls of the peripheral pulmonary arteries. Hypercapnia inhibits release of both oxygen radicals and nitric oxide at the beginning of exposure to the hypoxic environment. The plasma concentration of nitrotyrosine, the marker of peroxynitrite activity, is lower in hypoxic rats exposed to hypercapnia than in those exposed to hypoxia alone. Hypercapnia blunts hypoxia-induced collagenolysis in the walls of prealveolar pulmonary arteries. We conclude that hypercapnia inhibits the development of hypoxic pulmonary hypertension by the inhibition of radical injury to the walls of peripheral pulmonary arteries., M. Chovanec ... [et al.]., and Obsahuje seznam literatury
Hyperinflation is the consequence of a dysbalance of static forces (determining the relaxation volume) and/or of the dynamic components. The relaxation volume is determined by an equilibrium between the elastic recoil of the lungs and of the chest walls. The dynamic components include the pattern of breathing, upper airway resistance and postinspiratory activity of inspiratory muscles. The respiratory and laryngeal muscles are under control and thus both static and dynamic hyperinflation can be secured. Our knowledge of the mechanism of increased FRC is based on clinical observations and on experiments. The most frequent stimuli leading to a dynamic increase of functional residual lung capacity (FRC) include hypoxia and vagus afferentation. Regulation of FRC is still and undetermined concept. The controlled increase of FRC, hyperinflation, participates in a number of lung diseases., F. Paleček., and Obsahuje bibliografii
We investigated the influence of oxygenation of in vitro lung preparation on the pulmonary vascular reactivity. Small pulmonary vessels isolated from adult male Wistar rats exposed for 4 days to hypoxia (FiO2 = 0.1, group CH) were compared with those of normoxic controls (group N). The bath in the chamber of small vessel myograph was saturated with gas mixture containing either 21 % or 95 % of O2 with 5 % CO2 and we measured the reactions of vessels to acute hypoxic challenge with 0 % O2 or to PGF2α. We did not observe any difference of the contractile responses between both groups when the normoxic conditions were set in the bath. When the bath oxygenation was increased to 95 % O2, the contractions induced by hypoxic challenge and PGF2α decreased in chronically hypoxic rats and did not change in normoxic controls. We hypothesize that reduced reactivity of vessels from hypoxic rats in hyperoxia results from the effect of chronic hypoxia on Ca2+ signaling in the vascular smooth muscle, which is modulated by increased free radical production during the exposure to chronic hypoxia and further hyperoxia., M. Žaloudíková, M. Vízek, J. Herget., and Obsahuje seznam literatury
Experimental pneumonia induced by intratracheal application of carrageenan or paraquat increases the functional residual lung capacity (FRC) in rats. The mechanism of this increase is not clear, but a decrease in PO2 may be involved. To test this possibility, we attempted to eliminate the PO2 decrease in carrageenan-treated rats by exposing them to hyperoxia. Animals of the first group were exposed to 7 days of hyperoxia (FIO2 0.78-0.84, group Car+O2) after intratracheal application of carrageenan (0.5 ml of 0.7 % carageenan in saline), whereas animals of the second group were given the same dose of carrageenan but breathed air (group Car+A). The third group of rats was kept for seven days in hyperoxia (group O2) and the fourth group served as controls (C). The animals were then anesthetized and intubated and their ventilatory parameters and FRC were measured during air breathing. Carrageenan application induced a FRC increase (Car+A 2.0±0.2 ml, C 1.6±0.1 ml), which was not seen in carrageenan-treated rats exposed to hyperoxia (Car+O2 1.6±0.1 ml). Hyperoxia alone did not affect the value of FRC (O2 1.5±0.1 ml). These results support the hypothesis that a decrease in PO2 plays an important role in the carrageenan-induced increase of FRC in rats., B. Fišárková, M. Vízek., and Obsahuje bibliografii
M1-muscarinic acetylcholine (ACh) receptors (M1R) were directly demonstrated immunocytochemic ally in electronmicroscopic images of rat diaphragm neuromus cular junctions (NMJ). Specific electron-dense granules were located at presynaptic nerve ending membranes and in the sa rcolemma in the depths of postsynaptic folds. This first visualization of M1R on both sides of the NMJ is in agreement with previous pharmacological data on the regulatory role of M1R in quantal and non-quantal ACh release. and Obsahuje bibliografii a bibliografické odkazy
The impact of high -intensity exercise on disease progression and muscle contractile properties in experimental autoimmune encephalomyelitis (EAE) remains unclear. Control (CON) and EAE rats were divided into sedentary and exercise groups. Before onset (experiment 1, n=40) and after hindquarter paralysis (experiment 2, n=40), isokinetic foot extensor strength, cross sectional area (CSA) of tibialis anterior (TA), extensor digitorum longus (EDL) and soleus (SOL) and brain -derived neurotrophic factor (BDNF) levels were assessed. EAE reduced muscle fiber CSA of TA, EDL and SOL. In general, exercise was not able to affect CSA, whereas it delayed hindquarter paralysis peak. CON muscle work peaked and declined, while it r emained stable in EAE. BDNF -responses were not affected by EAE or exercise. In conclusion, EAE affected CSA -properties of TA, EDL and SOL, which could, partly, explain the absence of peak work during isokinetic muscle performance in EAE -animals. However, exercise was not able to prevent muscle fiber atrophy., I. Wens, U. Dalgas, K. Verboven, L. Kosten, A. Stevens, N. Hens, B. O. Eijnde., and Obsahuje bibliografii
Blood pressure (BP) level results from the balance of vasoconstrictors (mainly sympathetic nervous system) and vasodilators (predominantly nitric oxide and endothelium-derived hyperpolarizing factor). Most of the forms of experimental hypertension are associated with sympathetic hyperactivity and endothelial dysfunction. It is evident that nitric oxide and norepinephrine are antagonists in the control of calcium influx through L-type voltage-dependent calcium channels (L-VDCC). Their effects on L-VDCC are mediated by cGMP and cAMP, respectively. Nevertheless, it remains to determine whether these cyclic nucleotides have direct effects on L-VDCC or they act through a modulation of calcium-activated K+ and Cl- channels which influence membrane potential. Rats with genetic or salt hypertension are characterized by a relative (but not absolute) NO deficiency compared to the absolute enhancement of sympathetic vasoconstriction. This dysbalance of vasoconstrictor and vasodilator systems in hypertensive animals is reflected by greater calcium influx through L-VDCC susceptible to the inhibition by nifedipine. However, when the modulatory influence of cyclic nucleotides is largely attenuated by simultaneous ganglionic blockade and NO synthase inhibition, BP of spontaneously hypertensive rats remains still elevated compared to normotensive rats due to augmented nifedipine-sensitive BP component. It remains to determine why calcium influx through L-VDCC of hypertensive rats is augmented even in the absence of modulatory influence of major vasoactive systems (sympathetic nervous system, nitric oxide)., M. Pintérová ... [et al.]., and Obsahuje seznam literatury