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
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
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
a1_The wide chemical diversity of estrogenic compounds precludes an accurate prediction of estrogenic activity on the basis of chemical structure or radioimmunological assay and thus requires that the potency of these compounds is defined by bioassay. The mammary duct growth response in intact prepubertal and adult gonadectomized female and male mice of the C3H/Di strain was used to assess the estrogenicity of synthetic compounds or their derivatives. The vehicle for tested compounds should be free of estrogenic and other hormonal effects. Olive oil or sunflower oil exerted estrogenic activities and were thus unsuitable as vehicles for the tested compounds. The absence of estrogenic activity, high solubility of different steroid hormones, and the low incidence of the inflammatory reactions at the injection site were achieved by using a vehicle containing benzyl alcohol, benzyl benzoate, butylhydroxyanisole, butylhydroxytoluene, ethyl oleate and ethanol. The bioassay was primarily designed to examine the effect of tested compounds on mammogenesis. The duration of hormone treatment was chosen to be long enough for induction of duct growth but too short to induce lobuloalveolar differentiation. Females were treated for 10 days, males for 15 days. The proportional volume occupied by mammary epithelial structures was estimated by the modified Chalkley's technique. The mean coefficient of variation of quantitative evaluation of 10 different mammary glands obtained by two operators varied between 3.2 and 17.4 %. The mean coefficient of variation of quintuplicate determinations of each mammary gland by one operator was 10.1 %, and 11.1 % by the other. The correlation coefficient between results of two operators was 0.994. Estrogens are primarily defined by their ability to increase the mitotic activity of female secondary sex organs., a2_However, our results have shown that progesterone alone, if administered in a high dose, stimulates mammary growth in both intact prepubertal and OV-X female mice similarly as the synthetic progestatial steroid norethindrone with inherent estrogenic properties. In contrast, progesterone alone had no effect, in young intact or adult castrated males, but norethindrone did stimulate mammary growth. These results demonstrated that the mammary gland of males is a suitable model for estrogen screening., J. Škarda., and Obsahuje bibliografii
The aim of our study was to investigate adrenocortical function in the context of disease activity and inflammatory status in premenopausal RA females. Adrenal glucocorticoid and androgen responses to the 1 μg ACTH 1-24 test were investigated in 23 premenopausal RA and in 15 age- and BMI-matched healthy females. Twelve RA patients were on low-dose prednisone (<8.5 mg/day). Patients with DAS28>3.2 had lower (p<0.05) total plasma cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone and androstenedione responses in the ACTH test compared to healthy controls. Patients with DAS28>3.2 had lower (p<0.05) dehydroepiandrosterone response in the ACTH test compared to patients with DAS28≤3.2. C-reactive protein (CRP), DAS28, and interleukin (IL)-6 negatively correlated with androstenedione response to ACTH 1-24. Responses of all measured adrenal steroids were lower (p<0.05) in patients on low-dose glucocorticoids compared to healthy controls. RA patients not treated with glucocorticoids had lower total cortisol response (p=0.038) but did not differ in free plasma cortisol in the ACTH test. The results indicate an association of increased disease activity with a decrease in adrenal androgen production in RA and normal cortisol bioavailability in patients not treated with glucocorticoids., R. Imrich, M. Vlcek, J. Kerlik, M. Vogeser, F. Kirchhoff, A. Penesova, Z. Radikova, J. Lukac, J. Rovensky., and Obsahuje bibliografii