The effects of gemfibrozil (GFZ), an antihyperlipidemic agent, on the anionic transport of the human red blood cells (RBC) during the oxygenation-deoxygenation cycle were examined. Gemfibrozil clearly plays a role in the modulation of the anionic flux in erythrocytes; in fact it causes a strong increment of anions transport when the RBCs are in the high-oxygenation state (HOS). Such an effect is remarkably reduced in the low-oxygenation state (LOS). With the aim of identifying the dynamics of fibrate action, this effect has been investigated also in human ghost and chicken erythrocytes. These latter, in fact, are known to possess a B3 (anion transporter or Band 3) modified at the cytoplasmic domain (cdb3) which plays a significant role in the metabolic modulation of red blood cells. The results were analyzed taking into account the well-known interactions between fibrates and both conformational states of hemoglobin i.e. the T state (deoxy-conformation) and the R state (oxy-conformation). The effect of gemfibrozil on anionic influx appears to be due to a wide interaction involving a “multimeric” Hb-GFZ-cdb3 macromolecular complex. and Obsahuje bibliografii a bibliografické odkazy
Surgical Plethysmographic Index (SPI), calculated from pulse photo-plethysmographic amplitude oscillations, has been proposed as a tool to measure nociception anti-nociception balance during general anesthesia, but it is affected by several confounding factor that alter the autonomic nervous system (ANS) modulation. We hypothesized that SPI may be mainly affected by sympathetic stimulation independently from nociception. We studied the effects of two sympathetic stimuli on SPI, delivered through passive head-up tilt at 45 and 90 degrees angles, in nine awake healthy adults. The sympathetic modulation was assessed by means of heart rate variability (HRV) analysis. Mean (SD) SPI significantly increased from baseline to 45 degrees [from 38.6 (13.7) to 60.8 (7.6), p<0.001)] and to 90 degrees angle tilt [82.3 (5.4), p<0.001]. The electrocardiographic mean R-to-R interval significantly shortened during both passive tilts, whereas systolic arterial pressure did not change during the study protocol. HRV changed significantly during the study protocol towards a predominance of sympathetic modulation during passive tilt. Gravitational sympathetic stimulation at two increasing angles, in absence of any painful stimuli, affects SPI in awake healthy volunteers. SPI seems to reflect the sympathetic outflow directed to peripheral vessels., R. Colombo, A. Marchi, B. Borghi, T. Fossali, E. Tobaldini, S. Guzzetti, F. Raimondi., and Obsahuje bibliografii
A low birth weight is a new risk factor for the development of premature atherosclerosis. The effect of intrauterine undernutrition on hypercholesterolemia in later life was studied in an experimental model using the Prague Hereditary Hypercholesterolemic (PHHC) rat. Compared to animals in the control group (Wistar rats), animals with an increased sensitivity to high-cholesterol diet (PHHC rats) display hypercholesterolemia. Only in PHHC animals, individuals undernourished in their intrauterine life (hypotrophic group, HG) had a significantly higher total cholesterol, compared with individuals without food restriction in pregnancy (eutrophic group, EG). Restricted food intake in pregnancy led to smaller nests and a decreased number of pups in each litter. We found no significant diferences in birth weight between HG and EG. In spite of similar birth weights in PHHC and Wistar rats, intrauterine undernutrition caused an increase in cholesterolemia in the HG group of the PHHC rats. The effect of intrauterine undernutrition on the development of hypercholesterolemia will most likely play a role in individuals with geneticaly determined increased susceptibility to a high-cholesterol diet. The use of this model of intrauterine undernutrition for the study of hypercholesterolemia has proved to be feasible., P. Szitányi, J. Hanzlová, R. Poledne., and Obsahuje bibliografii
In healthy subjects, the right ventricular filling pattern estimated from tricuspid valve inflow is highly load-dependent. This can be clearly demonstrated by changes of Doppler inflow tracings recorded during tidal breathing at rest. The aim of our study was to test the magnitude of tricuspid inflow changes during more pronounced load changes induced by specific maneuvers. In 31 apparently healthy subjects (16 men and 15 women, mean age 36±16 years) we recorded pulsed Doppler tracings of tricuspid inflow during forced inspiration, elevation of lower extremities (increased preload) and handgrip exercise (increased afterload). The obtained values were compared with end-expiratory phase of tidal breathing at rest. We found a significantly larger increase in the early and late filling velocities (for E and A p<0.001) under the conditions of increasing preload (elevation of legs) and less pronounced, but still significant changes with isometric exercise (for E p<0.001 and for A p<0.01). We conclude that the right ventricular filling pattern in healthy humans is highly load-sensitive and for this reason the effect of any intervention (e.g. pharmacological) must be studied under strict and well-defined resting conditions., E. Mandysová, P. Niederle., and Obsahuje bibliografii a bibliografické odkazy
Consumption of seafood containing toxin domoic acid (DA) causes an alteration of glutamatergic signaling pathways and could lead to various signs of neurotoxicity in animals and humans. Neonatal treatment with domoic acid was suggested as valuable model of schizophrenia and epilepsy. We tested how repeated early postnatal DA administration influences the spontaneous behavior of rats in adulthood. Rats were injected with 30 μg DA/kg from postnatal day (PND) 10 until PND 14. Their behavior was observed in the open field test for one hour (Laboras, Metris) at PND 35, PND 42 and PND 112. We did not find any difference between DA treated rats and animals injected with equivalent volume of saline in both test sessions at PND 35 and PND 42. DA rats at PND 112 exhibited significantly higher vertical and horizontal exploratory activity (tested parameters: locomotion, distance travelled, average speed reached during test, grooming and rearing) between the 30th-40th min of the test session and habituated over 10 min later. We conclude that at least in the given experimental design, neonatal DA treatment results in alteration of the spontaneous behavior of rats in adulthood., K. Jandová, P. Kozler, M. Langmeier, D. Marešová, J. Pokorný, V. Riljak., and Obsahuje bibliografii
Photothrombotic model of ischemia (PT) is based on free radical-mediated endothelial dysfunction followed by thrombosis. Free radicals are also involved in hypoxic preconditioning. We tested the sensitivity of PT to preconditioning with hypobaric hypoxia and to pretreatment with melatonin. In adult Wistar rats, after intravenous application of Rose Bengal, a stereo-tactically defined spot on the denuded skull was irradiated by a laser for 9 min. The first experimental group underwent hypobaric hypoxia three days before irradiation. In the second experimental group, melatonin was applied intraperitoneally one hour before irradiation. Three days after irradiation, animals were sacrificed, the brains perfused, and stained with TTC. Ischemic lesions were divided into grades (I, II, III). In the control group (where no manipulation preceded photothrombosis), most animals displayed deep damage involving the striatum (grade III). The group pre-exposed to hypoxia showed similar results. Only 28.57 % of the melatonin pretreated animals exhibited grade III lesions, and in 57.14 % no signs of lesions were detected. Pre-exposure to hypoxia was not protective in our model. Pretreatment with melatonin lead to a significant reduction of the number of large ischemic lesions. This result is probably caused by protection of endothelial cells by melatonin., I. Matějovská, K. Bernášková, D. Krýsl, J. Mareš., and Obsahuje bibliografii a bibliografické odkazy
An ethanol vapor concentration of 1.6 mmol/l was used to test the diurnal variations of the olfactory response in two groups of snails, which were adapted to different light-dark cycles. The results revealed that the olfactory sensitivity to stimulation with ethanol was significantly increased during the day-time, which corresponds to the scotophase of the light-dark cycle, to which the animals had been adapted (c2-test, P < 0.01)., M. Voss, C. Büchert, C. Missfelder., and Obsahuje bibliografii
PPAR-α agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-α agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-α agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-α expression in human liver and muscle., K. Anderlová, R. Doležalová, J. Housová, L. Bošanská, D. Haluzíková, J. Křemen, J. Škrha, M. Haluzík., and Obsahuje bibliografii a bibiografické odkazy
Inhibin B is a gonadal dimeric polypeptide hormone that regulates synthesis and secretion of follicle stimulating hormone (FSH) in a negative feedback loop. The aim of the present study was to determine changes in serum inhibin B, gonadotropins and testosterone concentrations during childhood and puberty in males. We studied the relationship between circulating inhibin B, gonadotropins and testosterone in serum of healthy boys during the first two years of life and then in pubertal development. Using a recently developed two-side enzyme-linked immunosorbent assay (ELISA), inhibin B levels were measured in the serum of 78 healthy boys divided into eleven age groups from birth to the end of pubertal development. In addition, serum levels of gonadotropins and testosterone were measured. Serum inhibin B, gonadotropins and testosterone increased during the first months of postnatal life. A peak in serum inhibin B and gonadotropins concentrations was observed around 3-4 months of age. There was a significant positive correlation between serum inhibin B and gonadotropins and testosterone levels during the first 2 years of life. After this early increase, serum inhibin B, gonadotropins and testosterone levels decreased significantly and remained low until puberty followed by an increase beginning with the onset of puberty. Serum levels of inhibin B reached a peak at stage G3 of puberty. Around midpuberty, inhibin B lost its positive correlation with luteinizing hormone (LH) and testosterone from early puberty, and developed a strong negative correlation with FSH, which persisted into adulthood. We conclude that inhibin B plays a key role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis during male childhood and pubertal development. Inhibin B is a direct marker of the presence and function of Sertoli cells and appears to reflect testicular function in boys., M. Chada, R. Průša, J. Bronský, K. Kotaška, K. Šídlová, M. Pechová, L. Lisá., and Obsahuje bibliografii
a1_Inhibin B, produced by granulosa cells in the ovary, is a heterodimeric glycoprotein suppressing synthesis and secretion of the follicle stimulating hormone (FSH). The aim of the present study was to determine hormone profiles of inhibin B, FSH, luteinizing hormone (LH), and estradiol in girls during childhood and puberty and to evaluate whether inhibin B is a marker of follicle development. We examined the correlation between inhibin B and gonadotropins and estradiol during the first two years and across the pubertal development. Using a specific two-side enzyme-linked immunosorbent assay (ELISA), inhibin B levels were measured in the serum of 53 healthy girls divided into 8 groups according to age. In addition, serum FSH, LH, and estradiol were measured by chemiluminescent immunoassay in all serum samples. A rise in serum levels of inhibin B (55.2±7.3 ng/l, mean ± S.E.M.) and FSH (1.78±0.26 UI/l), concomitant with a moderate increment of serum LH (0.36±0.09 UI/l) and estradiol (45.8±12.2 pmol/l) concentrations was observed during the first three months of life and declined to prepubertal concentrations thereafter. A strong positive correlation between inhibin B and FSH (r = 0.48, p<0.05), LH (r = 0.68, p<0.001) and estradiol (r = 0.59, p<0.01) was demonstrated during the first 2 years of life. A rise in serum levels of inhibin B, FSH, LH, and estradiol was found throughout puberty. Inhibin B had a strong positive correlation with FSH (stage I of puberty: r = 0.64, p<0.05; stage II of puberty: r = 0.86, p<0.01), LH (I: r = 0.61, p<0.05; II: r = 0.67, p<0.05), and estradiol (II: r = 0.62, p<0.05) in early puberty. From pubertal stage II, inhibin B lost this relationship to gonadotropins and estradiol. Serum inhibin B and FSH levels increased significantly during pubertal development, with the highest peak found in stage III of puberty (133.5±14.3 ng/l), and decreased thereafter., a2_In conclusion, inhibin B is produced in a specific pattern in response to gonadotropin stimulation and plays an important role in the regulation of the hypothalamic-pituitary-gonadal axis during childhood and puberty in girls. Inhibin B is involved in regulatory functions in developing follicles and seems to be a sensitive marker of ovarian follicle development., M. Chada, R. Průša, J. Bronský, M. Pechová, L. Lisá., and Obsahuje bibliografii