The skeleton shows an unconventional role in the physiology and pathophysiology of the human organism, not only as the target tissue for a number of systemic hormones, but also as endocrine tissue modulating some skeletal and extraskeletal systems. From this point of view, the principal cells in the skeleton are osteocytes. These cells primarily work as mechano-sensors and modulate bone remodeling. Mechanically unloaded osteocytes synthetize sclerostin, the strong inhibitor of bone formation and RANKL, the strong activator of bone resorption. Osteocytes also express hormonally active vitamin D (1,25(OH)2D) and phosphatonins, such as FGF23. Both 1,25(OH)2D and FGF23 have been identified as powerful regulators of the phosphate metabolism, including in chronic kidney disease. Further endocrine cells of the skeleton involved in bone remodeling are osteoblasts. While FGF23 targets the kidney and parathyroid glands to control metabolism of vitamin D and phosphates, osteoblasts express osteocalcin, which through GPRC6A receptors modulates beta cells of the pancreatic islets, muscle, adipose tissue, brain and testes. This article reviews some knowledge concerning the interaction between the bone hormonal network and phosphate or energy homeostasis and/or male reproduction., I. Zofkova., and Obsahuje bibliografii
In the last decade a growing body of data revealed that the cerebellum is involved in the regulation of the affective reactions as well as in forming the associ ation between sensory stimuli and their emotional values. In humans, cerebellar areas around the vermis are activated during mental recall of emotional personal episodes and during learning of a CS-US association. Lesions of the cerebellar vermis may affect retention of a fear memory without altering baseline motor/autonomic responses to the frightening stimuli in both human and animal models. Reversible inactivation of the vermis during the consolidation period impairs retention of fear memory in rodents. Recent findings demonstrate that long-term potentiation (LTP) of synapses in the cerebellar cortex occurs in relati on to associative fear learning similar to previously reported data in the hippocampus and amygdala. Plastic changes affect both excitatory and inhibitory synapses. This concomitant potentiation allows the cerebellar cortical network to detect co incident inputs, presumably conveying sensorial stimuli, with better efficacy by keeping the time resolution of the system unchanged. Collectively, these data suggest that the vermis participates in forming new CS-US association and translate an emotional stat e elaborated elsewhere into autonomic and motor responses., P. Strata, B. Scelfo, B. Sacchetti., and Obsahuje bibliografii a bibliografické odkazy
Membrane fluidity is a widely recognized biophysical variable that provides information about structural organization of the subcellular membranes exhibiting physical characteristics of liquid crystals. The term “fluidity” reflects in this case the tightness in packing of acyl parts of the membrane phospholipid molecules, a feature that may influence considerably the molecular mobility and via that also the sensitivity and reactivity of membranebound transporters, receptors and enzyme systems. Data presented in this review are aimed to demonstrate the substantial role of changes in membrane fluidity occurring in the processes associated with endogenous protection observed in cardiac sarcolemma and mitochondria in diverse pathologies, particularly in diabetes and hypertension., A. Ziegelhöffer, ... [et al.]., and Obsahuje seznam literatury
In experimental and human diabetes mellitus, evidence for an impaired function of the vascular endothelium has been found and has been suggested to contribute to the development of vascular complications in this disease. The aim of the study was to evaluate possible regional hemodynamic in vivo differences between healthy and diabetic rats which would involve nitric oxide (NO). Central hemodynamics and regional blood flow (RBF) were studied using radioactive microspheres in early streptozotocin (STZ)-diabetic rats and compared to findings in healthy control animals. This method provides a possibility to study the total blood flow and vascular resistance (VR) in several different organs simultaneously. L-NAME iv induced widespread vasoconstriction to a similar extent in both groups. In the masseter muscle of both groups, acetylcholine 2 μg/kg per min, induced a RBF increase, which was abolished by pretreatment with L-NAME, suggesting NO as a mediator of vasodilation. In the heart muscle of both groups, acetylcholine alone was without effect while the combined infusion of acetylcholine and L-arginine induced an L-NAME-sensitive increase in RBF. The vasodilation induced by high-dose acetylcholine (10 μg/kg per min) in the kidney was more pronounced in the STZ-diabetic rats. The results indicate no reduction in basal vasodilating NO-tone in the circulation of early diabetic rats. The sensitivity to vasodilating effects of acetylcholine at the level of small resistance arterioles vary between tissues but was not impaired in the diabetic rats. In the heart muscle the availability of L-arginine was found to limit the vasodilatory effect of acetylcholine in both healthy and diabetic rats. In conclusion, the results indicate a normal action of NO in the investigated tissues of the early STZ-diabetic rat., E. Granstam, S.-O. Granstam., and Obsahuje bibliografii
The mechanism of action by which insulin increases phosphatidic acid (PA) and diacylglycerol (DAG) levels was investigated in cultured hepatoma cells (HEPG2). Insulin stimulated phosphatidylcholine (PC) and phosphatidyl-inositol (PI) degradation through the activation of specific phospholipases C (PLC). The DAG increase appears to be biphasic. The early DAG production seems to be due to PI breakdown, probably through phosphatidyl-inositol-3-kinase (PI3K) involvement, whereas the delayed DAG increase is derived directly from the PC-PLC activity. The absence of phospholipase D (PLD) involvement was confirmed by the lack of PC-derived phosphatidylethanol production. Experiments performed in the presence of R59022, an inhibitor of DAG-kinase, indicated that PA release is the result of the DAG-kinase activity on the DAG produced in the early phase of insulin action., R. Novotná, P. de Vito, L. Currado, P. Luly, P. M. Baldini., and Obsahuje bibliografii
Continuous normobaric hypoxia (CNH) renders the heart more tolerant to acute ischemia/reperfusion injury. Protein kinase C (PKC) is an important component of the protective signaling pathway, but the contribution of individual PKC isoforms under different hypoxic conditions is poorly understood. The aim of this study was to analyze the expression of PKCε after the adaptation to CNH and to clarify its role in increased cardiac ischemic tolerance with the use of PKCε inhibitory peptide KP-1633. Adult male Wistar rats were exposed to CNH (10 % O2, 3 weeks) or kept under normoxic conditions. The protein level of PKCε and its phosphorylated form was analyzed by Western blot in homogenate, cytosolic and particulate fractions; the expression of PKCε mRNA was measured by RT-PCR. The effect of KP-1633 on cell viability and lactate dehydrogenase (LDH) release was analyzed after 25-min metabolic inhibition followed by 30-min reenergization in freshly isolated left ventricular myocytes. Adaptation to CNH increased myocardial PKCε at protein and mRNA levels. The application of KP-1633 blunted the hypoxiainduced salutary effects on cell viability and LDH release, while control peptide KP-1723 had no effect. This study indicates that PKCε is involved in the cardioprotective mechanism induced by CNH., K. Holzerová, M. Hlaváčková, J. Žurmanová, G. Borchert, J. Neckář, F. Kolář, F. Novák, O. Nováková., and Obsahuje bibliografii
Here we studied whether descending control of mechanical nociception by glutamate in the central nucleus of the amygdala (CeA) of healthy control animals is induced by amygdaloid NMDA receptors and relayed through the midbrain periaqueductal gray (PAG). Mechanical nociception in the hind paws was assessed in rats with chronic guide cannulae for glutamate administration in the right CeA and for inducing local anesthesia in the PAG. In a separate electrophysiological study, ON-like PAG neurons giving an excitatory response to noxious pinch of the tail were recorded in anesthetized rats following glutamate administration into the CeA. A high dose of glutamate (100 μg) in the CeA induced mechanical antinociception in the contra- but not ipsilateral hind limb. Antinociception was prevented by an NMDA receptor antagonist in the CeA or local anesthesia of the PAG. Discharge rate of ON-like PAG neurons was increased by a high dose of glutamate (100 μg) in the CeA and this increase was prevented by an NMDA receptor antagonist in the CeA. The results indicate that amygdaloid NMDA receptors in the CeA may induce contralaterally mechanical antinociception through a circuitry relaying in the PAG. Activation of ON-like PAG neurons is associated with the descending antinociceptive effect. Mechanisms and causality of this association still remain to be studied., N. Bourbia, A. Pertovaara., and Obsahuje bibliografii
Iodine is essential in the biosynthesis of thyroid hormones that affect metabolic processes in the organism from the prenatal state to the elderly. The immediate indicator of iodine intake is the concentration of iodine in urine, but the indicator of iodine intake in the longer term of several months is thyroglobulin (Tg). Tg negatively correlated with increasing intake of iodine in population that do not suffer from thyroid disease, while a more than adequate to excessive iodine intake leads to an increase in Tg. The dependence of Tg on iodine can be described by a U-shaped curve. Thyroglobulin in serum is elevated in thyroid disease mainly in hyperthyroidism (diagnosis E05 of WHO ICD-10 codes) and in goiter (diagnosis E04 of WHO ICD-10 codes). Tg values decrease below 20 µg/l after effective treatment of patients with thyroid disease. Thyroglobulin may thus be an indicator of thyroid stabilization and the success of the thyroid gland treatment., Radovan Bílek, Marcela Dvořáková, Tereza Grimmichová, Jan Jiskra., and Obsahuje bibliografii
Osteoprotegerin (OPG) plays an important inhibitory role in osteoclastogenesis. Polymorphisms in the OPG gene recently have been associated with various bone phenotypes including fractures. The aim of the present study was to investigate the association between three informative OPG polymorphisms and quantitative ultrasound variables of the heel. In a cohort of 165 perimenopausal women polymorphisms in the OPG promoter (A163G, T245G) and in exon 1 (G1181C) were assessed by PCR-RFLP analysis. The distribution of the investigated genotypes was similar to other Caucasian women (A163G-AA 68 %, AG 30 %, GG 2 %, T245G-TT 84.4 %, TG 15 %, GG 0.6 %, G1181C-GG 22 %, CG 55 %, CC 23 %). After adjustment for body mass index and years since menopause, in a subgroup of 87 postmenopausal subjects, calcaneal velocity of sound (VOS, m/s) was significantly associated with A163G polymorphism (p=0.0102, ANCOVA). Women with the presence of G allele (AG+GG genotypes) had significantly lower VOS than women with AA genotype. Neither T245G nor G1181C were associated with calcaneal ultrasound indices. In conclusion, A163G polymorphism was significantly associated with VOS at the heel in a limited cohort of postmenopausal women. The present study replicated in part the previous findings about OPG gene variations and peripheral bone mass in Caucasian women., K. Zajíčková, A. Zemanová, M. Hill, I. Žofková., and Obsahuje bibliografii a bibliografické odkazy
Carbon monoxide (CO) reversibly binds to hemoglobin forming carboxyhemoglobin (COHb). CO competes with O 2 for binding place in hemoglobin leading to tissue hypoxia. Already 30 % saturation of COHb can be deadly. Medical oxygen at atmospheric pressure as a therapy is not enough effective. Therefore hyperbaric oxygen O 2 inhalation is recommended. There was a question if partially ionized oxygen can be a better treatment at atmospheric pressure. In present study we evaluated effect of partially ionized oxygen produced by device Oxygen Ion 3000 by Dr. Engler in elimination of COHb in vitro experiments and in smokers. Diluted blood with different content of CO was purged with 5 l /min of either medicinal oxygen O 2 , negatively ionized O 2 or positively ionized O 2 for 15 min , then the COHb content was checked. In vivo study, 15 smokers inhaled o f either medicinal oxygen O 2 or negatively ionized O 2 , than we compared CO levels in expired air before and after inhalation. In both studies we found the highest elimination of CO when we used negatively ionized O 2 . These results confirmed the benefit of short inhalation of negatively ionized O 2 , in frame of Ionized Oxygen Therapy (IO 2 Th/Engler) which could be used in smokers for decreasing of COHb in blood., S. Perečinský, I. Kron, I. Engler, L. Murínová, V. Donič, M. Varga, A. Marossy, Ľ. Legáth., and Obsahuje bibliografii