Leptin, a cytokine-like hormone secreted by adipocytes, is known to regulate food intake but has also emerged as a significant factor in the regulation of bone mass. In humans, states of energy deprivation with low serum leptin have been associated with low bone mass. In mice, leptin deficiency led to increased trabecular bone mass with overall decrease in cortical bone. Leptin regulates bone metabolism indirectly in the hypothalamus thereby activating the sympathetic nervous system (SNS). In addition to the SNS, leptin also interacts with various hypothalamic neuropeptides, such as cocaine- and amphetamine-regulated transcript, neuropeptide Y and/or neuromedin U, which might modulate the effects of leptin on bone. In osteoblasts sympathetic signaling is further gated by the transcriptional factors called molecular clock. As a result, bone loss is accelerated showing that the central effect of leptin seems to be antiosteogenic. Additionally, leptin has a direct anabolic effect within the bone driving the differentiation of bone marrow stem cells into the osteoblastic cell lineage. Besides the interaction between the central and peripheral pathways, the overall effect of leptin on bone might be bimodal depending on leptin serum concentrations. Regulatory pathways triggering osteoblast activity might open new possibilities for anabolic treatment of osteoporosis., V. Cirmanová, M. Bayer, L. Stárka, K. Zajíčková., and Obsahuje bibliografii a bibliografické odkazy
In vitro models serve as a tool for studies of steatosis. Palmitic and oleic acids can induce steatosis in cultured hepatocytes. The aim of our study was to verify steatogenic and cytotoxic effects of palmitic acid (PA), oleic acid (OA) and their combinations as well as their impact on functional capacity of rat primary hepatocytes. Hepatocytes were exposed to OA or PA (0.125-2 mmol/l) or their combination at ratios of 3:1, 2:1 or 1:1 at the final concentrations of 0.5-1 mmol/l. Both OA and PA caused a dose-dependent increase in triacylglycerol content in hepatocytes. PA was more steatogenic at 0.25 and 0.5 mmol/l while OA at 0.75 and 1 mmol/l. PA exhibited a dose-dependent cytotoxic effect associated with ROS production, present markers of apoptosis and necrosis and a decrease in albumin production. OA induced a damage of the cytoplasmic membrane from 1 mM concentration. Mixture of OA and PA induced lower cytotoxicity with less weakened functional capacity than did PA alone. Extent of steatosis was comparable to that after exposure to OA alone. In conclusion, OA or combination of OA with PA is more suitable for simulation of simple steatosis than PA alone., A. Moravcová, Z. Červinková, O. Kučera, V. Mezera, D. Rychtrmoc, H. Lotková., and Obsahuje bibliografii
The brain is widely responsive to gonadal hormones. The functional significance of ovarian hormones in the brain is evident from biochemical studies indicating that estradiol or progesterone treatment of testectomized rats produces changes of antioxidant enzyme activities. The effect of estradiol benzoate (EB) and progesterone (P) in the control of antioxidant (AO) enzyme activities was studied in the brain of adult male Wistar rats. The activities of catalase (CAT), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) and glutathione reductase (GR) were measured in appropriate subcellular fractions, prepared from brains of animals belonging to various experimental groups. These groups were designed with the intention to follow changes in enzyme activities 2 h or 24 h after systemic administration of 5 g EB or 2 mg P to testectomized (TX) animals. The obtained results show that both EB and P increase CAT activity, whereas EB decreases GSH-Px, GST and GR activities. These findings clearly show the modulatory role of EB and P in the control of enzymes responsible for the protection of rat nerve cells against oxidative damage caused by free oxygen radicals., S. B. Pajović, Z. S. Saičić, M. B. Spasić, V. M. Petrović., and Obsahuje bibliografii
Protective effect of quercetin, a natural antioxidant compound, on hypericin-induced cytotoxicity was studied in human promyelocytic leukemia cells (HL-60). Hypericin (10-5 mol.l-1) alone significantly decreased cell survival to 21 % that found in the controls, whereas in combination with quercetin (10-5 mol.l-1) this decrease was diminished to 46 %. Lower concentrations of quercetin had no protective effect. These findings indicate that oxygen radicals can play an important role in hypericin-induced phototoxic effects., A. Miroššay, H. Onderková, L. Mirossay, M. Šarišský, J. Mojžiš., and Obsahuje bibliografii
A significant factor in the development of hypertension may be excessive vasoconstriction within the renal medulla. This study therefore investigated the role of superoxide dismutase (SOD) in the regulation of renal medullary and cortical blood perfusion (MBP and CBP, respectively) in both stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar rats. CBP and MBP were measured before and after intra-renal infusion of the SOD inhibitor, diethyldithio-carbamic acid (DETC). Under basal conditions, mean arterial pressure was significantly greater in SHRSP than Wistar rats, but both MBP and heart rate (HR) were significantly lower in SHRSP relative to Wistar rats (P<0.05, n=7 in both groups). Infusion of DETC (2 mg/kg/min) into the cortico-medullary border area of the kidney significantly decreased MBP in the SHRSPs (by 28±3 %, n=7, P<0.05), indicating a greater vasoconstriction within this vascular bed. However, DETC also significantly decreased MBP in Wistar rats to a similar extent (24±4 %, n=7, P<0.05). These results suggest that superoxide anions play a significant role in reducing renal vascular compliance within the renal medulla in both normotensive and hypertensive animals, although the responses are not greater in the hypertensive relative to the control animals., A. F. Ahmeda, M. G. Rae, L. M. Anweigi, M. F. Al Otaibi, A. A. Al-Masri, E. J. Johns., and Obsahuje bibliografii
Chronic kidney disease (CKD) is associated with increased concentration of intracellular calcium, which is pathological and may lead to irreversible damage of cell functions and structures. The aim of our study was to investigate the impact of 6 months vitamin D3 supplementation (14 000 IU/week) on free cytosolic calcium concentration ([Ca2+]i) and on the plasma membrane calcium ATPase (PMCA) activity of patients with CKD stage 2-3. PMCA activity of patients was also compared to that of healthy volunteers. Vitamin D3 supplementation of CKD patients resulted in the decrease of [Ca2+]i (119.79±5.87 nmol/l vs. 105.36± 3.59 nmol/l, n=14, P<0.001), whereas PMCA activity of CKD patients (38.75±22.89 nmol Pi/mg/h) remained unchanged after vitamin D3 supplementation (40.96±17.74 nmol Pi/mg/h, n=14). PMCA activity of early stage CKD patients before supplementation of vitamin D3, was reduced by 34 % (42.01±20.64 nmol Pi/mg/h) in comparison to healthy volunteers (63.68±20.32 nmol Pi/mg/h, n=28, P<0.001). These results indicate that vitamin D3 supplementation had a lowering effect on [Ca2+]i and negligible effect on PMCA activity in CKD patients., M. Morvová Jr., I. Lajdová, V. Spustová, M. Zvarík, L. Šikurová., and Obsahuje bibliografii
In cardiac surgical patients we investigated the effects of cardiopulmonary bypass (CPB) with a hollow fiber membrane oxygenator on blood clotting measured by thromboelastography (TEG). We found only a minimal change in the strength of blood clot described either by the TEG parameter MA (maximum amplitude) or by the shear modulus G calculated from MA. After CPB there was also a significant tendency towards hypercoagulation as defined by shortened parameters R, K and increased ?-angle. After comparison with published data obtained in cardiac surgical patients using a bubble oxygenator we conclude that currently used extracorporeal technology exerts a less negative influence on blood clotting than had been conceived previously., M. Horáček, K. Cvachovec., and Obsahuje bibliografii
The present study investigated the effects of head cooling during endurance cycling on performance and the serotonergic neuroendocrine response to exercise in the heat. Subjects exercised at 75 % VO2max to volitional fatigue on a cycle ergometer at an ambient temperature of 29±1.0 °C, with a relative humidity of approximately 50 %. Head cooling resulted in a 51 % (p<0.01) improvement in exercise time to fatigue and Borg Scale ratings of perceived exertion were significantly lower throughout the exercise period with cooling (p<0.01). There were no indications of peripheral mechanisms of fatigue either with, or without, head cooling, indicating the importance of central mechanisms. Exercise in the heat caused the release of prolactin in response to the rise in rectal temperature. Head cooling largely abolished the prolactin response while having no effect on rectal temperature. Tympanic temperature and sinus skin temperature were reduced by head cooling and remained low throughout the exercise. It is suggested that there is a co-ordinated response to exercise involving thermoregulation, neuroendocrine secretion and behavioural adaptations that may originate in the hypothalamus or associated areas of the brain. Our results are consistent with the effects of head cooling being mediated by both direct cooling of the brain and modified cerebral artery blood flow, but an action of peripheral thermoreceptors cannot be excluded., L. Ansley, G. Marvin, A. Sharma, M. J. Kendall, D. A. Jones, M. W. Bridge., and Obsahuje bibliografii a bibliografické odkazy
Cytochrome oxidase activity from the retina can be enhanced or depressed by free radical-mediated reactions both in positive and negative aspect. The greatest effect was exerted by ischemia/reperfusion, which significantly increased the fluorescent products of lipid peroxidation (358 %, P<0.01) and inhibited the enzyme activity (14 %, P<0.001). After hyperoxia the fluorescent products slightly increased (192 %, P< 0.05) as well as the enzyme activity (133 %, P<0.05). Hypoxia had no effect on any of these parameters. Specific changes in the composition of fluorophores after ischemia/reperfusion were revealed in the fluorescence spectra. The fact that increased lipid peroxidation after hyperoxia and after ischemia/reperfusion does not produce the same effect upon cytochrome oxidase activity might be explained by changes in the kinetic behavior of cytochrome oxidase. In the control enzyme preparation, two binding sites for cytochrome c were observed. One was of the low-affinity (Km=60 mM) and the other of the high-affinity (Km=1.12 mM). After in vitro-initiated lipid peroxidation, the low-affinity binding site was lost and the activity measured under "optimum" conditions at a single cytochrome concentration was higher than in the controls. This implies that oxidative damage to cytochrome oxidase in vivo can be site-specific and its extent should be estimated by performing detailed kinetic analysis as otherwise the results might be misleading., A. Šišková, J. Wilhelm., and Obsahuje bibliografii