The relative length of telomeres measured in peripheral blood leukocytes is a commonly used system marker for biological aging and can also be used as a biomarker of cardiovascular aging. However, to what extent the telomere length in peripheral leukocytes reflects telomere length in different organ tissues is still unclear. Therefore, we have measured relative telomere length (rTL) in twelve different human tissues (peripheral blood leukocytes, liver, kidney, heart, spleen, brain, skin, triceps, tongue mucosa, intercostal skeletal muscle, subcutaneous fat, and abdominal fat) from twelve cadavers (age range of 29 week of gestation to 88 years old). The highest rTL variability was observed in peripheral leukocytes, and the lowest variability was found in brain. We found a significant linear correlation between leukocyte rTL and both intercostal muscle (R=0.68, P<0.02) and liver rTL (R=0.60, P<0.05) only. High rTL variability was observed between different organs from one individual. Furthermore, we have shown that even slight DNA degradation (modeled by sonication of genomic DNA) leads to false rTL shortening. We conclude that the rTL in peripheral leukocytes is not strongly correlated with the rTL in different organs., D. Dlouha, J. Maluskova, I. Kralova Lesna, V. Lanska, J. A. Hubacek., and Obsahuje bibliografii
The objective of this study was to evaluate the influence of low-dose combined oral contraception (COC) on basal and stimulated (1 μg ACTH test) levels of serum and salivary cortisol (F), cortisone and on basal serum cortisol binding globulin (CBG), adrenocorticotropic hormone (ACTH), dehydroepiadrosterone (DHEA) and calculated free cortisol in healthy young women. Three-month administration of COC resulted in 1) significant increase of basal (454.0±125.0 to 860.9±179.7 nmol/l) and ACTH-stimulated serum cortisol in 30th min (652.3±60.5 to 1374.1±240.6 nmol/l); 2) no significant change of basal (15.4±7.3 to 18.9±8.5 nmol/l) and ACTH-stimulated salivary cortisol at the 30th min (32.4±8.8 to 32.9±9.0 nmol/l); 3) no significant change of basal serum cortisone (38,8±7.68 to 45.2±24.2 nmol/l) and ACTH-stimulated cortisone at the 30th (34.8±10.9 to 47.0±35.7 nmol/l); 4) significant increase of basal ACTH (17.2±9.0 to 38.2±29.4 ng/l), CBG (991.0±161.0 to 2332.0±428.0 nmol/l), and 5) no significant change of basal DHEA (24.6±15.7 to 22.6±11.7 μmol/l) and calculated basal value for free cortisol (22.8±14.9 to 19.2±6.9nmol/l). In conclusions, higher basal and ACTH-stimulated serum cortisol were found after three-month administration of COC, while basal and stimulated salivary cortisol were not significantly affected. Therefore, salivary cortisol can be used for assessment of adrenal function in women regularly using COC., K. Šimůnková, L. Stárka, M. Hill, L. Kříž, R. Hampl, K. Vondra., and Obsahuje bibliografii a bibliografické odkazy
This study investigated whether each part of the heart is evenly innervated by the left or right vagus and observed the mechanism of compensatory recovery after unilateral cervical vagotomy. HR, BP, LVSP and ±dp/dt max all decreased one week after left vagotomy, whereas only BP and -dp/dt max decreased one week after right vagotomy. We stern blot analyses revealed that the expression of M2 receptors in the left atrium and left ventricle was upregulated after subacute (1 week) left/right vagotomy. However, significantly more cholinesterase-positive nerves in LV and RV were seen one week after unilateral vagotomy compared to the sham-operated group. In addition, baroreflex sensitivity was increased after subacute right vagotomy. The decreasing effects of ACh (0.5 μ g/kg) on LVSP and ±dp/dt max (but not on HR and BP) were facilitated by subacute unilateral vagotomy. Our present experiments indicate that 1) the working myocardium is innervated bilaterally by the vagus, 2) ventricular contractility is influenced more by denervation of the left than the right vagus and 3) up-regulation of M2 muscarinic receptors in the left heart, increase of cholinergic nerves, and high baroreflex sensitivity could be involved in the mechanism of compensatory hemodynamic recovery via contralateral vagus overactivity, thereby amplifying contralateral vagal activity and decreasing cardiac contractility., L. N. Chen, W. J. Zang, X. J. Yu, J. Liu, D. L. Li, S. S. Kong, J. Lu, X. L. Xu., and Obsahuje bibliografii a bibliografické odkazy
The role of alkaloids in cigarette smoke was investigated in the cumulus expansion of oocyte-cumulus complexes (OCC) isolated from large antral porcine follicles. Suppression of the cumulus expansion stimulated by FSH was observed in the presence of different concentration of cadmium, anabasine and nicotine but not its metabolite cotinine. There were comparable inhibitory effects of cadmium and nicotine on the synthesis and accumulation of hyaluronic acid in the cell/matrix compartment of OCC. The inhibitory effect of tested compounds on the cumulus expansion was accompanied by decreased progesterone synthesis by cumulus cells during 42 h incubation of OCC with FSH. The results suggest that cigarette smoking may affect intrafollicular processes, which are responsible for normal ovulation and fertilization., S. Vršanská, E. Nagyová, A. Mlynarčíková, M. Ficková, J. Kolena., and Obsahuje bibliografii
E. Filová, M. Rampichová, M. Handl, A. Lytvynets, R. Halouzka, D. Usvald, J. Hlučilová, R. Procházka, M. Dezortová, E. Rolencová, E. Košťáková, T. Trč, E. Šťastný, L. Koláčná, M. Hájek, J. Motlík, E. Amler. and Obsahuje bibliografii
31P MR spectroscopy was used to measure the signal intensity ratios of high-energy metabolites for the calculation of free cytosolic magnesium concentration [fMg2+] and pH in the calf muscles of patients with primary juvenile hypertension and of healthy controls. Surface coil and spectroscopic imaging techniques were used. In patients with hypertension, the concentrations of [fMg2+] was 788±33 mmol/l and intracellular pH was 7.05±0.02; these values were not significantly different from the results obtained in healthy controls ([fMg2+], 776±21 mmol/l and pH, 7.06±0.01). Biochemical assays of magnesium in the serum (S-Mg) and in urine (DU-Mg) confirmed this finding. Significant differences in the relative signal intensities of high-energy phosphates between patients with primary juvenile hypertension and healthy controls were observed: a) signal intensity ratios of PCr/Pi, PCr/PbATP, PDE/PbATP were increased, and b) Pi/PDe, Pi/PATP were decreased. The results were the same irrespective of whether the surface coil method or 31P spectroscopic imaging were employed., M. Hájek, D. Palyzová, M. Kořínek, D. Kurková., and Obsahuje bibliografii
Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution., C. Vetter ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
We assessed the effect of the previously uncovered gap junctio n protein alpha 8 (Gja8) mutation present in spontaneously hypertensive rat - dominant cataract (SHR - Dca ) strain on blood pressure, metabolic profile, and heart and renal transcriptomes. Adult, standard chow-fed male rats of SHR and SHR - Dca strains were used. We found a significant, consistent 10-15 mmHg decrease in both systolic and diastolic blood pressures in SHR - Dca compared with SHR (P<0.01 and P<0.05 , respectively; repeated measures analysis of variance (ANOVA)). With immunohistochemistry, we were able to localize Gja8 in heart, kidney, aorta, liver, and lungs, mostly in endothelium; with no differences in expression between strains. SHR - Dca rats showed decreased body weight, high-density lipoprotein cholesterol concentrations and basa l insulin sensitivity in muscle. There were 21 transc ripts common to the sets of 303 transcripts in kidney and 487 in heart showing >1.2-fold difference in expression between SHR and SHR - Dca. Tumor necrosis factor was the most significant upstream regulato r and glial cell-derived neurotrophic factor family ligand-receptor interactions was the common enriched and downregulated canonical pathway both in heart and kidney of SHR - Dca. The connexin 50 mutation L7Q lowers blood pressure in the SHR - Dca strain, decr eases high-density lipoprotein cholesterol, and leads to substantial transcriptome changes in heart and kidney., O. Šeda, F. Liška, M. Pravenec, Z. Vernerová, L. Kazdová, D. Křenová, V. Zídek, L. Šedová, M. Krupková, V. Křen., and Obsahuje bibliografii
Muscarinic acetylcholine receptors in the heart have been shown to display agonist-independent spontaneous (constitutive) activity which causes changes in the opening of cardiac ion channels and in the activity of G proteins. We investigated whether an inhibition of the constitutive activity of muscarinic receptors induced by the binding of antagonist brings about a change in the synthesis of cyclic AMP in rat cardiac membranes, and whether the action of the antagonist is stereospecific. Atropine and S-(-)-hyoscyamine were indeed found to enhance the forskolin-stimulated synthesis of cyclic AMP in rat cardiac (both atrial and ventricular) membranes by up to 24%. The effect was stereospecific and the potency of R-(+)-hyoscyamine was 30 fold lower than that of the S-(-) enantiomer, confirming that the action of hyoscyamine is receptor-mediated. The effect did not depend on the presence of endogenous acetylcholine in the system used. The results strongly suggest that the adenylyl cyclase in the heart is exposed to continuous mild inhibition by constitutively active muscarinic receptors in the membranes of cardiomyocytes., J. Říčný, F. Gualtieri, S. Tuček., and Obsahuje bibliografii