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
a1_Progesterone and estradiol are the foremost steroid hormones in human pregnancy. However, the origin of maternal progesterone has still not been satisfactorily explained, despite the generally accepted opinion that maternal LDL-cholesterol is a single substrate for placental synthesis of maternal progesterone. The question remains why the levels of progesterone are substantially higher in fetal as opposed to maternal blood. Hence, the role of the fetal zone of fetal adrenal (FZFA) in the synthesis of progesterone precursors was addressed. The FZFA may be directly regulated by placental CRH inducing an excessive production of sulfated 3β-hydroxy-5-ene steroids such as sulfates of dehydroepiandrosterone (DHEAS) and pregnenolone (PregS). Due to their excellent solubility in plasma these conjugates are easily transported in excessive amounts to the placenta for further conversion to the sex hormones. While the significance of C19 3β-hydroxy-5-ene steroid sulfates originating in FZFA for placental estrogen formation is mostly recognized, the question “Which maternal and/or fetal functions may be served by excessive production of PregS in the FZFA?“ - still remains open. Our hypothesis is that, besides the necessity to synthesize de novo all the maternal progesterone from cholesterol, it may be more convenient to utilize the fetal PregS. The activities of sulfatase and 3β-hydroxysteroid dehydrogenase (3β-HSD) are substantially higher than the activity of cytochrome P450scc, which is rate-limiting for the placental progesterone synthesis from LDL-cholesterol. However, as in the case of progesterone synthesis from maternal LDL-cholesterol, the relative independence of progesterone levels on FZFA activity may be a consequence of substrate saturation of enzymes converting PregS to progesterone., a2_Some of the literature along with our current data (showing no correlation between fetal and maternal progesterone but significant partial correlations between fetal and maternal 20α-dihydroprogesterone (Prog20α) and between Prog20α and progesterone within the maternal blood) indicate that the localization of individual types of 17β-hydroxysteroid dehydrogenase is responsible for a higher proportion of estrone and progesterone in the fetus, but also a higher proportion of estradiol and Prog20α in maternal blood. Type 2 17β-hydroxysteroid dehydrogenase (17HSD2), which oxidizes estradiol to estrone and Prog20α to progesterone, is highly expressed in placental endothelial cells lining the fetal compartment. Alternatively, syncytium, which is directly in contact with maternal blood, produces high amounts of estradiol and Prog20α due to the effects of type 1, 5 and 7 17β-hydroxysteroid dehydrogenases (17HSD1, 17HSD5, and 17HSD7, respectively). The proposed mechanisms may serve the following functions: 1) providing substances which may influence the placental production of progesterone and synthesis of neuroprotective steroids in the fetus; and 2) creating hormonal milieu enabling control of the onset of labor., M. Hill ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
NO is the “hero” molecule of the last few decades. It is a ubiquitous and omnipotent radical with both hemodynamic and antiproliferative effects within the cardiovascular system. NO is an important counterregulatory factor for vasoconstrictors and growth promoting substances. Endothelial dysfunction with decreased NO production is related to many cardiovascular disorders, such as coronary artery disease, heart failure and hypertension. Despite the important role of NO within the circulation, there is only limited evidence in the form of large clinical trials that NO delivery can reduce cardiovascular morbidity and mortality. Thus, NO donors are not in the first line therapy in ischemic heart disease, heart failure or arterial hypertension and NO delivery is recommended only in particular clinical situations, when a well established treatment is contraindicated or has an insufficient effect. It is concluded that the insufficient NO production is the principal disorder in endothelial dysfunction, which is related to cardiovascular pathology with deteriorated prognosis, but the impact of therapeutically increased NO bioactivity on the morbidity and mortality is inferior to well established treatment with ACE-inhibitors, AT1 receptor blockers, beta-blockers, statins and certain antihypertensive drugs. There is little doubt that NO is king in the circulation, but kings seldom decide the battles., Fedor Šimko., and Obsahuje bibliografii
The goal of the study was to determine whether postconditioning protects against different ischemia durations in the rabbit. Rabbits were assigned to a 20-, 25-, 45- or 60-min coronary occlusion followed by 24-h of reperfusion. Rabbits received no further intervention (control) or were postconditioned with four cycles of 30-s occlusion and 30-s reperfusion after myocardial infarction. Plasma levels of troponin I were quantified throughout reperfusion. In control conditions, infarct sizes (% area at risk using triphenyltetrazolium chloride) after 20, 25, 45 and 60 min of coronary occlusions were 23±3, 51±4, 70±3 and 81±3 %, respectively. With 20 and 25 min occlusion, postconditioning reduced infarct size by 43±10 and 73±21 %, respectively. On the other hand, with 45 or 60 min occlusion, postconditioning had no significant effects on infarct size (61±3 and 80±2 % of area at risk). Preconditioning protocol was performed with 25- and 60-min coronary occlusion. As expected, preconditioning significantly reduced infarct size. In conclusion, in the rabbit, the cardioprotection afforded by postconditioning is limited to less than 45 min coronary occlusion., R. Létienne, Y. Calmettes, B. Le Grand., and Obsahuje seznam literatury
Pulmonary hypertension (PH) unresponsive to pharmacological intervention is considered a contraindication for orthotopic heart transplantation (OHTX) due to risk of postoperative right-heart failure. In this prospective study, we describe our experience with a treatment strategy of improving severe PH in heart transplant candidates by means of ventricular assist device (VAD) implantation and subs equent OHTX. In 11 heart transplantation candidates with severe PH unresponsive to pharmacological intervention we implanted VAD with the aim of achieving PH to values acceptable for OHTX. In all patients we observed significant drop in pulmonary pr essures, PVR and TPG (p<0.001 for all) 3 months after VAD implantation to values sufficient to allow OHTX. Seven patients underwent transplantation (mean duration of support 216 days) while none of patients suffered right-side heart failure in postoperative period. Two patients died after transplantation and five patients are living in very good condition with a mean duration of 286 days after OHTX. In our opinion, severe PH is not a contraindication for orthotopic heart transplantation any more., J. Kettner ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Interesting and stimulating data about the effect of the perivascular adipose tissue size on atherogenesis are based mainly on CT findings. We studied this topic by directly analyzing perivascular adipose tissue in explanted hearts from patients undergoing transplantation. Ninety -six consecutive patients were included, including 58 with atherosclerotic coronary heart disease (CHD) and 38 with dilation cardiomyo pathy (DCMP). The area of perivascular fat, area of the coronary artery wall, and ratio of CD68 -positive macrophages within the perivascular fat and within the vascular wall were quantified by immunohistochemistry. There was no significant difference in th e perivascular adipose tissue size between the two groups. Nevertheless, there was a significantly higher number of macrophages in the coronary arterial wall of CHD patients. In addition, we found a close relationship between the ratio of macrophages in th e arterial wall and adjacent perivascular adipose tissue in the CHD group, but not in the DCMP group . According to our data interaction between macrophages in the arterial wall and macrophages in surrounding adipose tissue could be more important mechanism of atherogenesis than the size of this tissue itself., I. Kralova Lesna, Z. Tonar, I. Malek, J. Maluskova, L. Nedorost, J. Pirk, J. Pitha, V. Lanska, R. Poledne., and Obsahuje bibliografii
There is accumulating evidence showing that ischemic preconditioning (PC) may lose its cardioprotective effect in the diseased states. The present study investigated whether PC can be effective in hypothyroidism, a clinical condition which is common and often accompanies cardiac diseases such as heart failure and myocardial infarction. Hypothyroidism was induced in rats by 3-week administration of 6n-propyl-2-thiouracil in water (0.05 %). Normal and hypothyroid hearts (HYPO) were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischemia and 45 min of reperfus ion. A preconditioning protocol (PC) was also applied prior to ischemia. HYPO hearts had significantly improved post-ischemic recovery of left ventricular developed pressure, end-diastolic pressure and reduced lactate dehydrogenase release. Furthermore, phospho-JNK and p38 MAPK levels after ischemia and reperfusion were 4.0 and 3.0 fold lower in HYPO as compared to normal hearts ( P<0.05). A different response to PC was observed in normal than in HYPO hearts. PC improved the post-ischemic recovery of function and reduced the extent of injury in normal hearts but had no additional effect on the hypothyroid hearts. This response, in the preconditioned normal hearts, resulted in 2.5 and 1.8 fold smaller expression of the phospho-JNK and phospho-p38 MAPK levels at the end of reperfusion, as compared to non-PC hearts ( P<0.05), while in HYPO hearts, no additional reduction in the phosphorylation of these kinases was observed after PC. Hypothyroid hearts appear to be tolerant to ischemia-reperfusion injury. This response may be, at least in part, due to the down-regulation of ischemia-reperfusion induced activation of JNKs and p38 MAPK kinases. PC is not associated with further reduction in the activation of these kinases in the hypothyroid hearts and fails to confer added protection in those hearts., I. Mourouzis ... [et al.]., and Obsahuje seznam literatury
Prolonged cultivation of separated rat lung mast cells (LMC) in vitro is necessary to better investigate a possible role of LMC in different stages of tissue remodeling induced by hypoxia. Rat lung mast cells (LMC) were sepa rated using a protocol including an improved proteolytic extracti on and two subsequent density gradient separations on Ficoll-P aque PLUS and a new generation of Percoll, i.e. Percoll PLUS. Instead of usual isotonic stock Percoll solution, an alternative “asymptotically isotonic” stock solution was more successful in our density separation of LMC on Percoll PLUS. Separated cells were cultivated for six days in media including stem cell factor, interleu kins IL-3 and IL-6, and one of two alternative mixtures of antibi otics. These cultivations were performed without any contaminatio n and with only rare changes in cell size and morphology. Model co-cultivation of two allogenic fractions of LMC often caused considerable rapid changes in cell morphology and size. In contrast to these observations no or rare morphological changes were found after cultivation under hypoxic conditions. In conclusions, we modified separation on Percoll PLUS to be widely used, altered LMC separation with respect to purposes of long-lasti ng cultivation and observed some model morphological changes of LMC., J. Kubrycht ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy