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
Previous studies revealed altered levels of the circulating insulin-like growth factor-I (IGF-I) and of its binding protein-3 (IGFBP-3) in subjects with coronary atherosclerosis, metabolic syndrome and premature atherosclerosis. Hyperlipidemia is a powerful risk factor of atherosclerosis. We expected IGF-I and IGFBP-3 alterations in subjects with moderate/severe hyperlipidemia but without any clinical manifestation of atherosclerosis. Total IGF-I and IGFBP-3 were assessed in 56 patients with mixed hyperlipidemia (MHL; cholesterol>6.0 mmol/l, triglycerides>2.0 mmol/l), in 33 patients with isolated hypercholesterolemia (IHC; cholesterol>6.0 mmol/l, triglycerides<2.0 mmol/l), and in 29 healthy controls (cholesterol<6.0 mmol/l, triglycerides<2.0 mmol/l). The molar ratio of IGF-I/IGFBP-3 was used as a measure of free IGF-I. IHC subjects differed from controls by lower total IGF-I (164±60 vs. 209±73 ng/ml, p=0.01) and IGF-I/IGFBP-3 ratio (0.14±0.05 vs. 0.17±0.04, p=0.04). Compared to controls, MHL subjects had lower total IGF-I (153±54 ng/ml, p=0.0002) and IGFBP-3 (2.8±0.6 mg/ml, p<0.0001), but higher IGF-I/IGFBP-3 ratio (0.25±0.06, p<0.0001). Differences remained significant after the adjustment for clinical and biochemical covariates, except for triglycerides. Patients with both IHC and MHL have lower total IGF-I compared to controls. The mechanism is presumably different in IHC and MHL. Because of prominent reduction of IGFBP-3 in patients with MHL, they have reduced total IGF-I despite the actual elevation IGF-I/IGFBP-3 ratio as a surrogate of free IGF-I., J. Malík, T. Štulc, D. Wichterle, V. Melenovský, E. Chytilová, Z. Lacinová, J. Marek, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
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
Dental enamel hypoplasia as an indicator of non-specific stress in population from Znojmo-Hradiště (a comparison between medieval and modern time population).
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