Anthracyclines, e.g. doxorubicin, pirarubicin, are widely used as cytostatic agents in the polymer nanotherapeutics designed for the highly effective antitumor therapy with reduced side effects. However, their precise dosage scheme needs to be optimized, which requires an accurate method for their quantification of the cellular level in vitro during nanocarrier development and in body fluids and tissues during testing in vivo. Various methods detecting the anthracycline content in biological samples have already been designed. most of them are highly demanding and they differ in exactness and reproducibility. The cellular uptake and localization is predominantly observed and determined by microscopy techniques, the anthracycline content is usually quantified by chromatographic analysis using fluorescence detection. We reviewed and compared published methods concerning the detection of anthracycline nanocarriers., E. Koziolova, O. Janouskova, P. Chytil, M. Studenovsky, L. Kostka, T. Etrych., and Obsahuje bibliografii
Although there are abundant data on ischemic postconditioning (IPoC) in the adult myocardium, this phenomenon has not yet been investigated in neonatal hearts. To examine possible protective effects of IPoC, rat hearts isolated on days 1, 4, 7 and 10 of po stnatal life were perfused according to Langendorff. Developed force (DF) of contraction was measured by an isometric force transducer. Hearts were exposed to 40 or 60 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC wa s induced by three cycles of 10, 30 or 60 s periods of global ischemia/reperfusion. To further determine the extent of ischemic injury, lactate dehydrogenase (LDH) release was measured in the coronary effluent. Tolerance to ischemia did not change from day 1 to day 4 but decreased to days 7 and 10. None of the postconditioning protocols tested led to significant protection on the day 10. Prolonging the period of sustained ischemia to 60 min on day 10 did not lead to better protection. The 3x30 s protocol wa s then evaluated on days 1, 4 and 7 without any significant effects. There were no significant differences in LDH release between postconditioned and control groups. It can be concluded that neonatal hearts cannot be protected by ischemic postconditioning during first 10 days of postnatal life. and J. Doul, Z. Charvátová, I. Ošťádalová, M. Kohutiar, H. Maxová, B. Ošťádal.
The present study investigated the effects of nesfatin-1 on gastric distension (GD)-responsive neurons via an interaction with corticotropin-releasing factor (CRF) receptor signaling in the ventromedial hypothalamic nucleus (VMH), and the potential regulation of these effects by hippocampal projections to VMH. Extracellular single-unit discharges were recorded in VHM following administration of nesfatin-1. The projection of nerve fibers and expression of nesfatin-1 were assessed by retrograde tracing and fluoro-immunohistochemical staining, respectively. Results showed that there were GD-responsive neurons in VMH; Nesfatin-1 administration and electrical stimulation of hippocampal CA1 sub-region altered the firing rate of these neurons. These changes could be partially blocked by pretreatment with the non-selective CRF antagonist astressin-B or an antibody to NUCB2/nesfatin-1. Electrolytic lesion of CA1 hippocampus reduced the effects of nesfatin-1 on VMH GD-responsive neuronal activity. These studies suggest that nesfatin-1 plays an important role in GD-responsive neuronal activity through interactions with CRF signaling pathways in VMH. The hippocampus may participate in the modulation of nesfatin-1-mediated effects in VMH., H. Feng, Q. Wang, F. Guo, X. Han, M. Pang, X. Sun, Y. Gong, L. Xu., and Obsahuje bibliografii
The maintenance of plasma sodium concentration within a narrow limit is crucial to life. When it differs from normal physiological patterns, several mechanisms are activated in order to restore body fluid homeostasis. Such mechanisms may be vegetative and/or behavioral, and several regions of the central nervous system (CNS) are involved in their triggering. Some of these are responsible for sensory pathways that per ceive a disturbance of the body fluid homeostasis and transmit information to other regions. These regions, in turn, initiate adequate adjustments in order to restore homeostasis. The main cardiovascular and autonomic responses to a change in plasma sodium concentration are: i) changes in arterial blood pressure and heart rate; ii) changes in sympathetic activity to the renal system in order to ensure adequate renal sodium excretion/absorption, and iii) the secretion of compounds involved in sodium ion home ostasis (ANP, Ang-II, and ADH, for example). Due to their cardiovascular effects, hypertonic saline solutions have been used to promote resuscitation in hemorrhagic patients, thereby increasing survival rates following trauma. In the present review, we exp ose and discuss the role of several CNS regions involved in body fluid homeostasis and the effects of acute and chronic hyperosmotic challenges., M. C. Dos Santos Moreira, L. M. Naves, S. M. Marques, E. F. Silva, A. C. S. Rebelo, E. Colombari, G. R. Pedrino., and Obsahuje bibliografii
Ionotropic glutamate receptors function can be affected by neurosteroids, both positively and negatively. N-methyl-D-aspartate (NMDA) receptor responses to exogenously applied glutamate are potentiated or inhibited (depending on the receptor subunit composition) by pregnenolone sulphate (PS) and inhibited by pregnenolone sulphate (3α5βS). While PS effect is most pronounced when its application precedes that of glutamate, 3α5βS only binds to receptors already activated. Synaptically activated NMDA receptors are inhibited by 3α5βS, though to a lesser extent than those tonically activated by exogenous glutamate. PS, on the other hand, shows virtually no effect on any of the models of synaptically activated NMDA receptors. The site of neurosteroid action at the receptor molecule has not yet been identified, however, the experiments indicate that there are at least two distinct extracellularly located binding sites for PS mediating its potentiating and inhibitory effects respectively. Experiments with chimeric receptors revealed the importance of the extracellular loop connecting the third and the fourth transmembrane domain of the receptor NR2 subunit for the neurosteroid action, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors are inhibited by both PS and 3α5βS. These neurosteroids also affect AMPA receptors-mediated synaptic transmission, however, in a rather indirect way, through presynaptically located targets of action., M. Sedláček, M. Kořínek, M. Petrovič, O. Cais, E. Adamusová, H. Chodounská, L. Vyklický Jr., and Obsahuje bibliografii a bibliografické odkazy
The availability of the human genome sequence and the recently completed draft sequences of two major mammalian model species, the mouse (Mus musculus) and the rat (Rattus norvegicus), allow researchers to apply novel approaches for gene identification and characterization, using methods of comparative and functional genomics. Recently, a new gene coding for apolipoprotein A-V was identified in the vicinity of APOA-I/C-III/A-IV cluster on human chromosome 11q23 by comparative sequencing method. In a relatively short time, compelling evidence accumulated for the substantial role of APOA-V in lipid metabolism. Studies in knock-out and transgenic mice revealed that its expression pattern correlates negatively with triglyceride levels. This observation was verified in human population studies in variety of ethnic and age groups. Several single nucleotide polymorphisms were described and particular SNP alleles and haplotypes in the APO A-V gene region were shown to be associated with dyslipidemia. The discovery and characterization of the APO A-V demonstrates current possibilities of the integrative approaches in biology, boosted by the available bioinformatic tools., O. Šeda, L. Šedová., and Obsahuje bibliografii
Bone metabolism is regulated by interaction between two skeletal cells – osteoclasts and osteoblasts. Function of these cells is controlled by a number of humoral factors, including neurohormones, which ensure equilibrium between bone resorption and bone formation. Influence of neurohormones on bone metabolism is often bimodal and depends on the tissue, in which the hormone is expressed. While hypothalamic beta-1 and beta-2-adrenergic systems stimulate bone formation, beta-2 receptors in bone tissue activate osteoclatogenesis and increases bone resorption. Chronic stimulation of peripheral beta-2 receptors is known to quicken bone loss and alter the mechanical quality of the skeleton. This is supported by the observation of a low incidence of hip fractures in patients treated with betablockers. A bimodal osteo-tropic effect has also been observed with serotonin. While serotonin synthetized in brain has osteo-anabolic effects, serotonin released from the duodenum inhibits osteoblast activity and decreases bone formation. On the other hand, both cannabinoid systems (CB1 receptors in the brain and CB2 in bone tissue) are unambiguously osteoprotective, especially with regard to the aging skeleton. Positive (protective) effects on bone have also been shown by some hypophyseal hormones, such as thyrotropin (which inhibits bone resorption) and adrenocorticotropic hormone and oxytocin, both of which stimulate bone formation. Low oxytocin levels have been shown to potentiate bone loss induced by hypoestrinism in postmenopausal women, as well as in girls with mental anorexia. In addition to reviewing neurohormones with anabolic effects, this article also reviews neurohormones with unambiguously catabolic effects on the skeleton, such as neuropeptide Y and neuromedin U. An important aim of research in this field is the synthesis of new molecules that can stimulate osteo-anabolic or inhibiting osteo-catabolic processes., I. Žofková, P. Matucha., and Obsahuje bibliografii
This study investigated whether endothelin (ET)-1-induced increase in myocardial distensibility is preserved in heart failure (HF) and whether it is modulated by nitric oxide (NO) and prostaglandins. New Zealand white rabbits were treated with doxorubicin (1 mg/kg, intravenously twice a week for 8 weeks, DOX-HF group) or saline (control group). Effects of ET-1 (0.1, 1, 10 nM) were tested in papillary muscles from the DOX-HF group and a control group in the presence of: i) intact endocardial endothelium (EE); ii) damaged EE; iii) NG-nitro-L-arginine (L-NNA; NO synthase inhibitor), and iv) indomethacin (INDO; cyclooxygenase inhibitor). In the presence of an intact EE, ET-1 promoted concentration-dependent positive inotropic and lusitropic effects that were maintained after damaging the EE, in the presence of L-NNA or INDO and in the DOX-HF Group. ET-1 reduced resting tension at the end of the isometric twitch (increased diastolic distensibility) by 3.2±1.3 %, 6.0±1.6 % and 8.8±2.7 % (at 0.1, 1 and 10 nM, respectively), in muscles with intact EE, effect that was completely abolished after damaging EE, in the presence of L-NNA or INDO or in the DOX-HF Group. This study demonstrated that the increase in myocardial distensibility induced by ET-1 is absent in HF and is dependent of NO and prostaglandin release., C. Brás-Silva, D. Monteiro-Sousa, A. J. Duarte, M. Guerra, A. P. Fontes-Sousa, C. Moura, J. C. Areias, A. F. Leite-Moreira., and Obsahuje bibliografii a bibliografické odkazy
A method using body surface potential maps for assessment of myocardium lesions with changed repolarization is presented and suitable mapping system is introduced. Differences between normal and altered QRST integral maps together with torso volume conductor model were used to determine the equivalent dipole representing the lesion. Performance of the method was studied on simulated data. Changed repolarization was modeled by shortening of myocyte action potentials in regions typical for stenosis of the main coronary arteries. The equivalent dipole estimated the positions of small lesions with a mean error of 9±4 mm (17±14 mm for larger transmural lesions). The subepicardial or subendocardial character of the lesions was reflected in the dipole orientation. Tests of the method on patients after myocardial infarction that underwent coronary intervention on a single coronary vessel showed that in 7 of 8 successfully treated patients the dipole position matched well with the treated vessel. A small dipole moment in another patient indicated unsuccessful treatment. The method was implemented in a new 128-channel mapping system. Its active electrodes, battery powered measuring unit and optical computer interface help to minimize noise in ECG and guarantee patient´s safety. The results suggest that the method and mapping system offer useful tools for noninvasive identification of local repolarization changes in the myocardium., M. Tyšler, P. Kneppo, M. Turzová, J. Švehlíková, S. Karas, E. Hebláková, K. Hána, S. Filipová., and Obsahuje bibliografii