The article gives an overview of developmental aspects of the ontogeny of pain both in experimental models and in children. The whole article is devoted to the ontogenesis in pain perception and the possible influence on it. The role of endogenous opioids on the development of pain and other important substances such as serotonin, nerve growth factor (NGF) and nicotine are mentioned. There are also important differences of the ontogenesis of thermal and mechanical nociceptive stimulation. The physiological and pathophysiological findings are the backgrounds for principles of treatment, taking into account the special status of analgesics during ontogeny. In particular there are mentioned the special effects of endogenous opioids and especially morphine. It describes the role of vitamin D and erythropoietin during the development of pain perception. This article also mentioned the critical developmental periods in relation to the perception of pain. The attention is paid to stress and immunological changes during the ontogeny of pain. Another important role is played by microglia. The work is concluded by some statements about the use of physiological and pathophysiological findings during the treatment of pain in pediatric practice. Codein analgesia is also described because codein starts to be very modern drug with the dependence., R. Rokyta, J. Fricová., and Obsahuje seznam literatury
b1_Large number of extracellular signals is received by plasma membrane receptors which, upon activation, transduce information into the target cell interior via trimeric G-proteins (GPCRs) and induce activation or inhibition of adenylyl cyclase enzyme activity (AC). Receptors for opioid drugs such as morphine ( μ-OR, δ-OR and κ-OR) belong to rhodopsin family of GPCRs. Our recent results indicated a specific up-regulation of AC I (8-fold) and AC II (2.5-fold) in plasma membranes (PM) isolated from rat brain cortex exposed to increasing doses of morphine (10-50 mg/kg) for 10 days. Increase of ACI and ACII represented the specific effect as the amount of ACIII-ACIX, prototypical PM marker Na, K-ATPase and trimeric G-protein α and β subunits was unchanged. The up-regulation of ACI and ACII faded away after 20 days since the last dose of morphine. Proteomic analysis of these PM indicated that the brain cortex of morphine-treated animals cannot be regarded as being adapted to this drug because significant up-regulation of proteins functionally related to oxidativ e stress and alteration of brain energy metabolism occurred. The number of δ-OR was increased 2-fold and their sensitivity to monovalent cations was altered. Characterization of δ-OR-G-protein coupling in model HEK293 cell line indicated high ability of lithium to support affinity of δ-OR response to agonist stimulation. Our studies of PM structure and function in context with desensitization of GPCRs action were extended by data indicating part icipation of cholesterol-enriched membrane domains in agonist-specific internalization of δ-OR. In HEK293 cells stably expressing δ-OR-G i 1 α fusion protein, depletion of PM cholesterol was associated with the decrease in affinity of G-protein response to agonist stimulation, whereas maximum response was unchanged., b2_drophobic interior of isolated PM became more “fluid”, chaotically organized and accessible to water molecules. Validity of this conclusion was supported by the analysis of an immediate PM environment of cholesterol molecules in living δ -OR-G i 1 α-HEK293 cells by fluorescent probes 22- and 25-NBD-cholesterol. The alteration of plasma membrane structure by cholesterol depletion made the membrane more hydrated. Unders tanding of the positive and negative feedback regulatory loops among different OR-initiated signaling cascades (μ-, δ -, and κ-OR) is crucial for understanding of the long-term mechanisms of drug addiction as the decrease in functional activity of μ-OR may be compensated by increase of δ-OR and/or κ-OR signaling., H. Ujčíková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Genetic factors may contribute to the differential response to opioids. The aim of this study was to evaluate the association between polymorphisms of μ1-opioid receptor gene OPRM1 (rs1799971), and P-glycoprotein transporter gene ABCB1 (rs1045642, rs2032582), and piritramide efficacy under postoperative patient-controlled analgesia (PCA). In 51 patients, OPRM1 variant was associated with decreased efficacy in early postoperative period evidenced by sum of pain intensity difference in the 0-6 h postoperative period (SPID0-6), (F=3.27, p=0.029). Mean (SD) SPID0-6 was observed in the 118AA genotype 22.9 (6.1) mm, which was significantly higher from the 118GG genotype 10.0 (4.4) mm, p=0.006. The lowest cumulative dose was recorded in 118AA genotype 19.1 (9.8) mg, which was significantly less than in the 118GG genotype group 36.6 (6.1) mg, p=0.017. Opioid-induced adverse effects were observed in 11, 30, and 100 % of patients in 118AA, 118AG, and 118GG genotype groups, respectively (p<0.05). Piritramide efficacy and safety was not significantly affected by ABCB1 (rs1045642, rs2032582) polymorphisms. Variant OPRM1 118G allele is associated with decreased acute postoperative pain relief after piritramide. Decreased efficacy leads to higher drug consumption under PCA settings, which however, does not fully compensate insufficient pain relief, but increases incidence of adverse effects., O. Bartošová, O. Polanecký, F. Perlík, S. Adámek, O. Slanař., and Obsahuje bibliografii
The determination of cytochrome c oxidase (COX) activity represents an important indicator for the evaluation of cell oxidative capacity. However, it has been shown repeatedly that different factors modify the rate of COX activity under various experimental conditions. The most important concern the ionic concentrations of the medium and the application of various detergents for the solubilization of mitochondrial membranes. We found the highest activity of COX in rat heart homogenates and mitochondria at 40-60 mM potassium phosphate. The rate of COX activity is dependent on the detergent/protein (P) ratio. Using n-dodecyl-b-D-maltoside (lauryl maltoside, LM) as the detergent, we obtained the highest activity at LM/P ratios of (50:100):1. By kinetic measurements of low-affinity binding sites in heart mitochondria, we found Vlim values of 4.3 and 22.2 mmol cytochrome c per min per mg P in the presence or absence of lauryl maltoside, respectively. The Km values were 16.7 mmol in the presence or absence of lauryl maltoside. Our results thus indicate that 1) the exact assessment of COX activity in heart homogenates and mitochondria requires the determination of optimum phosphate concentrations in the medium used, and 2) even small modifications of the experimental procedure may induce significant differences in the maximum values of COX activity., A. Stieglerová, Z. Drahota, B. Ošťádal, J. Houštěk., and Obsahuje bibliografii
Our study compared total C-peptide secretion after administration of whey proteins and whey proteins in combination with glucose with results of classical tests assessing beta cell function in the pancreas of healthy individuals. Eight young, healthy (7 males, 1 female; aged 20-26 years), nonobese (BMI: 17-25.9 kg/m2 ) participants with normal glucose tolerance underwent six C-peptide secretion tests. Three secretion tests measured C-peptide response to orally administered substances: whey proteins only (OWT), whey proteins with glucose (OWGT) and glucose only (OGTT); while three secretion tests measured C-peptide response to intravenously administered substances: arginine (AST), glucagon (GST) and glucose (IVGTT). OWT stimulated a greater (93 %, p<0.05) C-peptide response than AST and a 64 % smaller response (p<0.05) than OGTT. OWT also showed lower variability (p<0.05) in C-peptide responses compared to OWGT and OGTT. The greatest total C-peptide response was induced by OWGT (36 % higher than glucose). OWT consistently increased C-peptide concentrations with lower individual variability, while insignificantly increasing glucose levels. Results of this study suggest that both dietology and beta-cells capacity testing could take advantage of the unique property of whey proteins to induce C-peptide secretion., E. Wildová, ... [et al.]., and Obsahuje seznam literatury
Orexins (orexin A and B) are initially known to be a hypothalamic peptide critical for feeding and normal wakefulness. In addition, emerging evidence from behavioral tests suggests that orexins are also involved in the regulation of nociceptive processing, suggesting a novel potential therapeutic approach for pain treatment. Both spinal and supraspinal mechanisms appear to contribute to the role of orexin in nociception. In the spinal cord, dorsal root ganglion (DRG) neurons are primary afferent neurons that transmit peripheral stimuli to the pain-processing areas. Morphological results show that both orexin A and orexin-1 receptor are distributed in DRG neurons. Moreover, by using whole-cell patch-clamp recordings and calcium imaging measurements we found that orexin A induced excitability and intracellular calcium concentration elevation in the isolated rat DRG neurons, which was mainly dependent on the activation of spinal orexin-1 receptor. Based on these findings, we propose a hypothesis that the direct effect of orexin A on DRG neurons would represent a possible mechanism for the orexinergic modulation of spinal nociceptive transmission., J.-A. Yan, L. Ge, W. Huang, B. Song, X.-W. Chen, Z.-P. Yu., and Obsahuje bibliografii a bibliografické odkazy
Previous results have suggested that orexins causes a rise of intracellular free calcium ([Ca2+]i) in cultured rat dorsal root ganglion (DRG) neurons, implicating a role in nociception, but the underlying mechanism is unknown. Hence, the aim of the present study was to investigate whether the orexins-mediated signaling involves the PKC pathways in these sensory neurons. Cultured DRG neurons were loaded with 1 μmol Fura-2 AM and [Ca2+]i responses were quantified by the changes in 340/380 ratio using fluorescence imaging system. The orexin-1 receptor antagonist SB-334867-A (1 μM) inhibited the calcium responses to orexin-A and orexin-B (59.1±5.1 % vs. 200 nM orexin-A, n=8, and 67±3.8 % vs. 200 nM orexin-B, n=12, respectively). The PKC inhibitor chelerythrine (10 and 100 μM) significantly decreased the orexin-A (200 nM)-induced [Ca2+]i increase (59.4±4.8 % P<0.01, n=10 and 4.9±1.6 %, P<0.01, n=9) versus response to orexin-A). It was also found that chelerythrine dose-dependently inhibited the [Ca2+]i response to 200 nM orexin-B. In conclusion, our results suggest that orexins activate intracellular calcium signaling in cultured rat sensory neurons through PKC-dependent pathway, which may have important implications for nociceptive modulation and pain., M. Ozcan ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The microcirculation plays a crucial role in the interaction between blood and tissues both in physiological and pathophysiological states. Despite its critical role in numer ous diseases including diabetes, hypertension, sepsis or multiple organ failure, methods for direct visualization and quantitative assessm ent of human microcirculation at the bedside are limited. Orthogonal polarization spectral (OPS) imaging is a relatively new noninvasive method for assessment of human microcirculation without using fluorescent dyes. Recent clinical studies using OPS imaging in various pathological states have shown a wide spectrum of different clinical applications with evident impact on the diagnosis, treatment or prognosis assessment. Thus, there is a great effort to validate OPS imaging for various clinical purposes. The principles of OPS imaging, validation studies, its advantages, limitations, methods of quantitative assessment and current experience in clinical practice are discussed., V. Černý, Z. Turek, R. Pařízková., and Obsahuje bibliografii a bibliografické odkazy
It was hypothesized that an oscillation of tissue oxygen index (TOI) determined by near-infrared spectroscopy during recovery from exercise occurs due to feedback control of adenosine triphosphate and that frequency of the oscillation is affected by blood pH. In order to examine these hypotheses, we aimed 1) to determine whether there is an oscillation of TOI during recovery from exercise and 2) to determine the effect of blood pH on frequency of the oscillation of TOI. Three exercises were performed with exercise intensities of 30 % and 70 % peak oxygen uptake (Vo2peak) for 12 min and with exercise intensity of 70 % Vo2peak for 30 s. TOI during recovery from the exercise was analyzed by fast Fourier transform in order to obtain power spectra density (PSD). There was a significant difference in the frequency at which maximal PSD of TOI appeared (Fmax) between the exercises with 70 % Vo2peak for 12 min (0.0039±0 Hz) and for 30 s (0.0061±0.0028 Hz). However, there was no significant difference in Fmax between the exercises with 30 % (0.0043±0.0013 Hz) and with 70 % Vo2peak for 12 min despite differences in blood pH and blood lactate from the warmed fingertips. It is concluded that there was an oscillation in TOI during recovery from the three exercises. It was not clearly shown that there was an effect of blood pH on Fmax., T. Yano, R. Afroundeh, K. Shirakawa, C.-S. Lian, K. Shibata, Z. Xiao, T. Yunoki., and Obsahuje bibliografii
A mathematical description is presented of osmotic flows across both ideally semipermeable membranes and membranes permeable not only for the solvent but also for the solute. The principles of thermodynamics of irreversible processes used for the description are given and illustrated on the example of electroosmosis. Modern ideas about the physical basis of osmotic pressure on porous membranes are discussed and an experiment is described that models the processes of osmosis on a macroscopic level., K. Janáček, K. Sigler., and Obsahuje bibliografii