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
Impressive advances in molecular genetic techniques allow to analyze the effects of natural selection on the development of human genome. For example, the trend towards blonde hair and blue eyes was documented. The approach to analyze possible effects of natural selection on the evolution of recent phenotypes with high risk of cardiovascular disease has not been described yet. A possible effect on the evolution of two main risk factors - hypercholesterolemia and hypertension - is presented. The close relationship of non-HDL cholesterol blood concentration to the proportion of pro-inflammatory macrophages in human visceral adipose tissue might be a result of long-lasting natural selection. Individuals with higher proportion of this phenotype might also display a higher ability to fight infection, which was very common in human setting from prehistory until Middle Ages. Successful battle against infections increased the probability to survive till reproductive age. Similar hypothesis was proposed to explain frequent hypertension in African Americans. A long-lasting selection for higher ability to conserve sodium during long-term adaptation to low sodium intake and hot weather was followed by a short-term (but very hard) natural selection of individuals during transatlantic slave transport. Only those with very high capability to retain sodium were able to survive. Natural selection of phenotypes with high plasma cholesterol concentration and/or high blood pressure is recently potentiated by high-fat high-sodium diet and overnutrition. This hypothesis is also supported by the advantage of familial hypercholesterolemia in the 19th century (at the time of high infection disease mortality) in contrast to the disadvantage of familial hypercholesterolemia during the actual period of high cardiovascular disease mortality., R. Poledne, J. Zicha., and Seznam literatury
We analyzed human postural responses to muscle vibration applied at four different frequencies to lower leg muscles, the lateral gastrocnemius (GA) or tibialis anterior (TA) muscles. The muscle vibrations induced changes in postural orientation characterized by the center of pressure (CoP) on the force platform surface on which the subjects were standing. Unilateral vibratory stimulation of TA induced body leaning forward and in the direction of the stimulated leg. Unilateral vibration of GA muscles induced body tilting backwards and in the opposite direction of the stimulated leg. The time course of postural responses was similar and started within 1 s after the onset of vibration by a gradual body tilt. When a new slope of the body position was reached, oscillations of body alignment occurred. When the vibrations were discontinued, this was followed by rapid recovery of the initial body position. The relationship between the magnitude of the postural response and frequency of vibration differed between TA and GA. While the magnitude of postural responses to TA vibration increased approximately linearly in the 60-100 Hz range of vibration frequency, the magnitude of response to GA vibration increased linearly only at lower frequencies of 40-60 Hz. The direction of body tilt induced by muscle vibration did not depend on the vibration frequency., A. Polónyová, F. Hlavačka., and Obsahuje bibliografii
We analyzed the immune response to gliadin in suckling rats and rats hand-fed with an artificial milk formula, an animal model of gluten enteropathy. Animals of both groups were intragastrically given either gliadin or albumin (control animals) or gliadin from birth till day 55. When compared to the controls, spleen lymphocytes from both groups of gliadin-treated rats cultivated in vitro exhibited a significant increase of spontaneous 3H-thymidine incorporation. Moreover, the proliferation of spleen and mesenteric lymph node (MLN) lymhocytes from both groups of gliadin-treated suckling and hand-fed rats was specifically increased by the in vitro gliadin challenge. Spleen B cells from gliadin-treated rats spontaneously produced higher amounts of gliadin-specific antibodies than those from the controls, however, in vitro stimulation by gliadin caused no further increase in antibody production. Apoptotic DNA fragmentation in MLN cells was higher in gliadin-treated rats than in albumin-treated ones, independently of the milk diet during the suckling period., H. Kozáková, R. Štěpánková, L. Tučková, M. Šinkora, L. Jelínková, H. Tlaskalová-Hogenová., and Obsahuje bibliografii
Hypoxic exposure triggers a generation of reactive oxygen species that initiate free radical damage to the lung. Hydrogen peroxide is the product of alveolar macrophages detectable in the expired breath. We evaluated the significance of breath H2O2 concentration for the assessment of lung damage after hypoxic exposure and during posthypoxic period. Adult male rats were exposed to normobaric hypoxia (10 % O2) for 3 hours or 5 days. Immediately after the hypoxic exposure and then after 7 days or 14 days of air breathing, H2O2 was determined in the breath condensate and in isolated lung macrophages. Lipid peroxidation was measured in lung homogenates. Three-hour hypoxia did not cause immediate increase in the breath H2O2; 5-day hypoxia increased breath H2O2 level to 458 %. After 7 days of subsequent air breathing H2O2 was elevated in both groups exposed to hypoxia. Increased production of H2O2 by macrophages was observed after 5 days of hypoxia and during the 7 days of subsequent air breathing. Lipid peroxidation increased in the periods of enhanced H2O2 generation by macrophages. As the major increase (1040 %) in the breath H2O2 concentration found 7 days after 3 hours of hypoxia was not accompanied by lipid peroxidation, it can be concluded that the breath H2O2 is not a reliable indicator of lung oxidative damage., J. Wilhelm, M. Vaňková, H. Maxová, A. Šišková., and Obsahuje bibliografii
As a novel gasotrans mitter, h ydrogen sulfide (H 2 S) has vasodilating and antihypertensive effects in cardiovascular system. Thus, we hypothesized that H 2 S might have beneficial effects on thoracic endothelial function in two -kidney one -clip (2K1C) rats, a model of renovascular hypertension. Sodium hydrosulfide (NaHS , 56 μmol/kg /day ) was administrated intra - peritoneally from the third day after the 2K1C operation. Along with the development of hypertension, t he systolic blood pressure (SBP) was measured before the operation and each week thereafter. The oxidative stress wa s determined by measurement of malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity and protein expression of oxidative stress -related proteins (AT 1 R, NADPH oxidase subunits). Acetylcholine (ACh) -induced vasorelaxation and angiotensin I I (Ang II) -induced vasocontraction were performed on isolated thoracic aorta. The SBP w as significantly increased from the first week after operation , and was lowered by NaHS. NaHS supplementation ameliorated endothelial dysfunction. The protein expression of oxidative stress -related proteins were downregulated, while SOD activity upregulated. In conclusion, improvement of endothelial function is involved in the antihypertensive mechanism of H 2 S. The protective effect of H 2 S is attributable to suppression o f vascular oxidative stress that involves inhibition of Ang II -AT 1 R action, downregulation of oxidases, as well as upregulation of antioxidant enzyme., H. Xue, S. Zhou, L. Xiao, Q. Guo, S. Liu, Y. Wu., and Obsahuje bibliografii
There is evidence that a higher serum level of bilirubin (BIL) may be a protective factor for autoimmune diseases. We examined the effect of BIL supplementation in adjuvant-induced arthritis (AIA) where oxidative stress, inflammation and inadequate immune response are present. Male Lewis rats were randomized into groups: CO - control, AIA - untreated adjuvant-induced arthritis, AIA-BIL - adjuvant-induced arthritis administrated BIL (200 mg/kg b.w. daily i.p. during 14 days). Change of hind paw volume in the AIA-BIL group in comparison to the AIA group was significantly decreased after BIL administration. In CO and AIA groups we found almost untraceable levels of BIL. In the AIA-BIL group hyperbilirubinemia was observed. BIL administration significantly decreased plasma levels of C-reactive protein and ceruloplasmin in the AIA-BIL group in comparison to the AIA group. The values of white and red blood cells, hemoglobin and hematocrit were significantly decreased in AIA-BIL after BIL supplementation. Organs like spleen and thymus had a lower weight in AIA-BIL than in AIA. Histological findings showed decreased or even absent damage in hind paw joint of AIA-BIL animals. We observed an immunomodulatory effect of BIL on AIA development, which may also have a novel pharmacological impact., K. Bauerova, F. Drafi, V. Kuncirova, S. Ponist, D. Mihalova, P. Babal, T. Sykora., and Obsahuje bibliografii
The metabolic pathways that contribute to maintain serum calcium concentration in narrow physiological range include the bone remodeling process, intestinal absorption and renal tubule resorption. Dysbalance in t hese regulations may lead to hyper - or hypocalcemia. Hypercalcemia is a potentionally life -threatening and relatively common clinical problem, which is mostly associated with hyperparathyroidism and/or malignant diseases (90 %). Scarce causes of hypercalce mia involve renal failure, kidney transplantation, endocrinopathies, granulomatous diseases, and the long -term treatment with some pharmaceuticals (vitamin D, retinoic acid, lithium). Genetic causes of hypercalcemia involve familial hypocalciuric hypercalc emia associated with an inactivation mutation in the calcium sensing receptor gene and/or a mutation in the CYP24A1 gene. Furthermore, hypercalcemia accompanying primary hyperparathyroidism, which develops as part of multiple endocrine neoplasia (MEN1 and MEN2), is also genetically determined. In this review mechanisms of hypercalcemia are discussed. The objective of this article is a review of hypercalcemia obtained from a Medline bibliographic search., I. Žofková., and Obsahuje bibliografii
To determine whether changes in partial pressure of CO2 participate in mechanism enlarging the lung functional residual capacity (FRC) during chronic hypoxia, we measured FRC and ventilation in rats exposed either to poikilocapnic (group H, FIO2 0.1, FICO2 <0.01) or hypercapnic (group H+CO2, FIO2 0.1, FICO2 0.04-0.05) hypoxia for the three weeks and in the controls (group C) breathing air. At the end of exposure a body plethysmograph was used to measure ventilatory parameters (V´E, fR, VT) and FRC during air breathing and acute hypoxia (10 % O2 in N2). The exposure to hypoxia for three weeks increased FRC measured during air breathing in both experimental groups (H: 3.0±0.1 ml, H+CO2: 3.1±0.2 ml, C: 1.8±0.2 ml). During the following acute hypoxia, we observed a significant increase of FRC in the controls (3.2±0.2 ml) and in both experimental groups (H: 3.5±0.2 ml, H+CO2: 3.6±0.2 ml). Because chronic hypoxia combined with chronic hypercapnia and chronic poikilocapnic hypoxia induced the same increase of FRC, we conclude that hypercapnia did not participate in the FRC enlargement during chronic hypoxia., H. Maxová, M. Vízek., and Obsahuje bibliografii
The purpose of this study was to evaluate the effects of hyperglycemia on skeletal muscle recovery following disuseinduced muscle atrophy in rats. Wistar rats were grouped as streptozotocin-induced diabetic rats and non-diabetic rats. Both ankle joints of each rat were immobilized to induce atrophy of the gastrocnemius muscles. After two weeks of immobilization and an additional two weeks of recovery, tail blood and gastrocnemius muscles were isolated. Serial cross sections of muscles were stained for myosin ATPase (pH 4.5) and alkaline phosphatase activity. Serum insulin and muscle insulin-like growth factor-1 (IGF-1) levels were also measured. Serum insulin levels were significantly reduced in the diabetic rats compared to the non-diabetic controls. The diameters of type I, IIa, and IIb myofibers and capillary-to-myofiber ratio in the isolated muscle tissue were decreased after immobilization in both treatments. During the recovery period, these parameters were restored in the non-diabetic rats, but not in the diabetic rats. In addition, muscle IGF-1 levels after recovery increased significantly in the non-diabetic rats, but not in the diabetic rats. We conclude that decreased levels of insulin and IGF-1 and impairment of angiogenesis associated with diabetes might be partly responsible for the inhibition of regrowth in diabetic muscle., H. Kataoka, J. Nakano, Y. Morimoto, Y. Honda, J. Sakamoto, T. Origuchi, M. Okita, T. Yoshimura., and Obsahuje bibliografii