Dehydroepiandrosterone (DHEA) and its sulphate-bound form (DHEAS) are important steroids mainly of adrenal origin. Their physiological and pathophysiological functions are not yet fully identified, although a number of various possible features have been hypothesized. Most popular is the description of the “hormone of youth” as the long-term dynamics of DHEA levels are characterized by a sharp age-related decline in the late adulthood and later. Low levels of DHEA are, however, associated not only with the ageing process but also with diabetes mellitus, cardiovascular diseases and some neurological or immunological entities. In the past decade, a number of brief studies have concentrated on these relationships and also on the role of exogenous DHEA in health, disease and human well-being. This article tries to summarize some of the most important facts achieved recently., P. Celec, L. Stárka., and Obsahuje bibliografii
This study aimed to examine relationships between DHEA(S), anthropometric parameters, oral glucose tolerance test derived data and lipid spectra in a Czech non-diabetic population. 380 healthy volunteers both with and without a family history of diabetes type 2 (DM2) were en rolled into the study (women: n=235, age 28.9±9.4 years, BMI 22.3±4.5 kg/m2, men: n=145, age 32.3±10.0 years, BMI 24.7±3.6 kg/m2). Spearman’s correlations (both without and with the adjustment for age, age and BMI), as well as ANCOVA were used. Non-adjusted data showed many “beneficial” correlations between DHEA(S) and both anthropometric and metabolic variables. Statistical analysis revealed that almost all correlations of DHEA(S) to adiposity and fat distribution in men as well as in women disappeared after the adjustment. There are, however, differences between men and women in the correlation of DHEA(S) to insulin sensitivity and lipid levels. The use of hormonal contraceptives (COC) is also an important factor in this relationship. In men and also in women using COC, DHEA-S after adjustment correlated positively with fasting and stimulated glucose, insulin and C-peptide, and negatively with insulin sensitivity. In this respect, the benefit of DHEA(S) supplementation seems - at least in terms of its alleged antiobesity and antidiabetogenic effects - to be more than controversial., B. Bendlová, J. Vrbíková, M. Hill, M. Vaňková, P. Lukášová, J. Včelák, D. Vejražková, K. Dvořáková, R. Hampl, K. Vondra, L. Stárka., and Obsahuje bibliografii a bibliografické odkazy
We studied delayed effects of elevated plasma levels of corticosterone (Cort) on volumetry, neuronal quantity, and gross marks of neurodegeneration in the hippocampal formation of Long-Evans rats. Animals were exposed to increased CORT levels for three weeks via implanted subcutaneous pellets. Volumetry, neuronal quantification and gros s marks of degeneration were measured seven weeks after the termination of CORT treatment. We observed significant differences in volumes and especially in laterality of hippocampal subfields between control and CORT- treated animals. We found th at the left hippocampus was substantially larger than the right hippocampus in the corticosterone-treated group, but not in the control group. In the control group, on the other hand, right hippocampal volume was markedly higher than all other measured volumes (hippocampal left control, hippocampal left CORT-treated and hippocampal right CORT-treated). Left hippocampal volume did not differ between the groups., P. Zach, J. Mrzílková, L. Řezáčová, A. Stuchlík, K. Valeš., and Obsahuje bibliografii
Dendritic cell (DC) vaccination is an attractive approach to the treatment of patients with lymphoid tumors. To evaluate its feasibility, we have tested the functional properties of DC and T-lymphocytes in patients with treated and untreated chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). Healthy volunteers were used both as controls and as a source of cells for allogeneic mixed leukocyte reaction (MLR). In these reactions, dendritic cells from both untreated and treated patients were comparable to dendritic cells from healthy volunteers. In all the untreated patients studied, autologous dendritic cells promoted the survival and proliferation of both CD4 and CD8 lymphocytes (though the proliferation response was much better in the CD4 subset), whereas only 3 out of 5 treated patients were able to mount this response with CD4 lymphocytes and 4 out of 5 with CD8 lymphocytes. In 3 out of 5 untreated patients, pulsing of DCs with tetanus toxoid promoted a better CD4 response than was achieved with unpulsed DCs, while none of 5 treated patients had an additional response after pulsing with tetanus toxoid. None of patients studied, either treated or untreated, had a better CD8 response to pulsed DCs than to unpulsed ones. During CD4 lymphocyte proliferation, more CD4+CD25hi lymphocytes were generated in both treated and untreated patients than in healthy controls. Poor proliferation of cytotoxic cells and preferential proliferation of CD4+CD25hi T-regulatory cells in response to self and/or foreign antigens might be one of the mechanisms responsible for immunosuppression and impaired tumor surveillance in patients with lymphoid malignancies., R. Pytlík, P. Hofman, L. Kideryová, P. Červinková, P. Obrtlíková, J. Šálková, M. Trněný, P. Klener., and Obsahuje bibliografii a bibliografické odkazy
All secretory anterior pituitary cells fire action potentials spontaneously and exhibit a high resting cation conductance, but the channels involved in the background permeability have not been identified. In cultured lactotrophs and immortalized GH3 cells, replacement of extracellular Na+ with large organic cations, but not blockade of voltage-gated Na+ influx, led to an instantaneous hyperpolarization of cell membranes that was associated with a cessation of spontaneous firing. When cells were clamped at –50 mV, which was close to the resting membrane potential in these cells, replacement of bath Na+ with organic cations resulted in an outward-like current, reflecting an inhibition of the inward holding membrane current and indicating loss of a background-depolarizing conductance. Quantitative RTPCR analysis revealed the high expression of mRNA transcripts for TRPC1 and much lower expression of TRPC6 in both lactotrophs and GH3 cells. Very low expression of TRPC3, TRPC4, and TRPC5 mRNA transcripts were also present in pituitary but not GH3 cells. 2-APB and SKF-96365, relatively selective blockers of TRPC channels, inhibited electrical activity, Ca2+ influx and prolactin release in a concentration-dependent manner. Gd3+, a common Ca2+ channel blocker, and flufenamic acid, an inhibitor of non-selective cation channels, also inhibited electrical activity, Ca2+ influx and prolactin release. These results indicate that nonselective cation channels, presumably belonging to the TRPC family, contribute to the background depolarizing conductance and firing of action potentials with consequent contribution to Ca2+ influx and hormone release in lactotrophs and GH3 cells., M. Kučka ... [et al.]., and Obsahuje seznam literatury
Index of vulnerability is a parameter based on ventricular gradient evaluating the risk of arrhythmia development. The index is derived from isointegral maps of the QT interval. Individual characteristics of isointegral maps are influenced by different factors, which contribute to the relatively high variability among measured parameters of maps in measured subjects. While several electrocardiographic indexes have been introduced, there are only few studies of their dependence on heart rate. In this study we set out to establish the dependence of vulnerability index on the RR interval or heart rate in healthy population. A positive linear correlation between RR intervals and mean and minimum values of vulnerability indexes was found., J. Martinka, K. Kozlíková., and Obsahuje bibliografii
Lithium-pilocarpine status epilepticus (SE) resulted in delayed changes of single cortical in terhemisperic (transcallosal) responses in immature rats. Low-frequency stimulation inducing depression and/or potentiation was studied to analyze possible dynamic changes in cortical responses. Status was elicited in 12-day-old (SE12) or 25-day-old (SE25) rats. Control siblings received saline instead of pilocarpine. Interhemispheric responses were elicited by stimulation of the sensorimotor region of the cerebral cortex 3, 6, 9, 13, or 26 days after status. A series of 5 biphasic pulses with intensity equal to twofold threshold were used for stimulation. The interval between pulses was 100, 125, 160, 200 or 300 ms, eight responses were always averaged. Peak amplitude of the first positive, first negative and second positive waves was measured and responses to the second, third, fourth and fifth pulse were compared with the first one. Animals after status epilepticus as well as lithium-paraldehyde controls exhibit a frequency depression at nearly all the intervals studied. An outlined increase of responses in SE rats in comparison with the controls three days after SE stayed just below the level of statistical significance. In addition, animals in the SE12 group exhibited potentiation of responses at this interval after SE. With longer intervals after SE, the relation between SE and control animals changed twice resulting in a tendency to lower amplitude of responses in SE than in control rats 26 days after SE. Rats in the SE25 group exhibited higher responses than controls 13 days after status, but this difference was not present at the longest interval after SE. Low-frequency stimulation did not reveal increased cortical excitability as a long-lasting consequence of status epilepticus induced in immature rats. In addition, the outlined differences between SE and control rats changed with the time after SE., G. Tsenov, P. Mareš., and Obsahuje bibliografii a bibliografické odkazy
A measuring system evaluating a Point Spread Function generated in an ultrasonographic image by scanning a spherical target was developed. The target is moved in measuring bath filled by water over scanned volume via 3D computer controlled positioning system. A video signal obtained is converted to digital form and analyzed by original software to derive various objective parameters of the imager as follows: Focal areas in both the azimuth and the elevation directions, Ultrasound scanning lines visualisation, Manufacturer preloaded TGC, Width of the scanning plane, Side lobe levels and Amplification uniformity in the azimuth direction. The method was verified by testing 18 different equipments in 282 measurements. Samples of particular measurement results in form of graphical outputs are included. Medical and physiological impacts of this approach are discussed., L. Doležal, J. Mazura, J. Tesařík, H. Kolářová, D. Korpas, S. Binder, J. Hálek., and Obsahuje bibliografii
The relationship between angiotensin II (ANG II) and endothelin-1 (ET-1) is known to be complex; both peptides can initiate and potentiate the gene expression of each other. This pilot study investigated the effects of the AT1 receptor blocker losartan or the direct renin inhibitor aliskiren on mean arterial pressure (MAP) and albuminuria and the renal ANG II and ET-1 levels. 3-month-old male Ren-2 transgenic rats (TGR) were treated either with losartan (5 mg kg-1 day-1) or aliskiren (10 mg kg-1 day-1) for 10 weeks. At the end of the experiment, rats were decapitated and cortical and papillary parts of kidneys were separated. Plasma and tissue ANG II levels were measured by RIA and tissue ET-1 concentrations by ELISA. In all four groups of animals ET-1 levels were lowest in renal cortex and more than 100-fold higher in the papilla. Cortical and papillary ET-1 concentrations in untreated TGR significantly exceeded those of control HanSD rats and were significantly depressed by both drugs. In both strains, papillary ANG II concentrations were moderately but significantly higher than cortical ANG II, TGR exhibited higher ANG II levels both in cortex and papilla as compared to control HanSD rats. Aliskiren and losartan at the doses used depressed similarly the levels of ANG II in cortex and papilla and reduced ET-1 significantly in the renal cortex and papilla below control levels in HanSD rats. Albuminuria, which was more than twice as high in TGR as in HanSD rats, was normalized with aliskiren and reduced by 28 % with losartan, although MAP was reduced to a similar degree by both drugs. Despite similar reductions of MAP and renal ET-1 and ANG II levels aliskiren appears to be more effective than losartan, at the doses used, in reducing albuminuria in heterozygous hypertensive Ren-2 rats., Z. Vaňourková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Recent observations suggest the presence of 20S proteasomes (20S) in the lung epithelial lining fluid. However, the physiological relevance of 20S in the alveolar space and possible contribution to disease processes are unknown. Thus, we evaluated whether extracellular proteasomes could have a pathophysiological role in the injured lung using a rat model of lung contusion (LC). Bronchoalveolar lavage fluids (BALF) were obtained at various time points for up to 168 h after LC or sham procedure. Enzyme activities, ELISA and Western blots indicated enzymatically active 20S, the 19S subunit Rpt5 and ubiquitin in BALF. 20S and ubiquitin increased significantl y after LC, peaked at 24 h and normalized within 168 h. Mg 2+ /ATP-dependent peptidase activities were detectable 6-24 h after LC. BALF after LC also contained ubiquitin-protein-ligase activity. Addition of Mg 2+ /ATP to BALF after LC led to significant proteolysis and could be prevented with epoxomicin and EDTA. These data suggest for the first time that the Mg 2+ /ATP-dependent 26S proteasome complex exists outside the cell, is released into the lung epithelial lining fluid after LC and contribute s to the proteolysis of the bulk of protein in the alveolar space of the injured lung. We infer that proteasome complexes may have a pathophysiological role during lung edema clearance., M. Majetschak, L. T. Sorell, T. Patricelli, D. H. Seitz, M. W. Knöferl., and Obsahuje bibliografii