There is an overlap of carrier-mediated L-amino acid transport and apparent simple diffusion when measured in intestinal brush border membrane vesicles. Using L-threonine and L-glutamine as representative amino acids, this study was undertaken to estimate apparent simple diffusion of L-amino acids and to establish the effective dosage of HgCl2 for completely blocking carrier-mediated L-amino acid transport in porcine jejunal enterocyte brush border membrane vesicles. Jejunal mucosa was scraped from three pigs weighing 26 kg. Enterocyte brush border membrane vesicles, with an average enrichment of 24-fold in sucrase specific activity, were prepared by Mg2+-precipitation and differential centrifugation. In vitro uptake was measured by the fast filtration manual procedure. HgCl2 blocked the carrier-mediated initial transport of L-threonine and L-glutamine under Na+-gradient condition in a dose-dependent manner. At the minimal concentration of 0.165 mmol HgCl2 mg-1 protein, carrier-mediated L-threonine and L-glutamine transport was completely inhibited. The apparent L-threonine and L-glutamine diffusion was estimated to be 8.6±0.7 and 12.4±1.0 % of the total uptake at the substrate concentrations of 5 mM (L-threonine) and 50 mM (L-glutamine). Therefore, the treatment of porcine brush border membrane vesicles with a minimum of 0.165 mmol HgCl2 mg-1 protein completely blocks carrier-mediated L-amino acid transport and enables the direct estimation of apparent L-amino acid diffusion in enterocyte brush border membrane vesicles., M. Z. Fan, O. Adeola, E. K. Asem., and Obsahuje bibliografii
Obesity increases the incidence of hypogonadism in men, and hypogonadism in turn plays a role in obesity. One of the first mechanisms proposed to explain this was a hypothesis based on the principle that obese men have higher estrogen levels, and that increased estrogens provide feedback to the hypothalamicpituitary-testicular axis, reducing the secretion of gonadotropins and leading to a decrease of overall testosterone levels. This concept has since been questioned, though never completely disproven. In this study we compared hormone levels in three groups of men with differing BMI levels (between 18-25, 25-29, and 30-39), and found correlations between lowering overall testosterone, SHBG and increased BMI. At the same time, there were no significant changes to levels of free androgens, estradiol or the gonadotropins LH and FSH. These findings are in line with the idea that estrogen production in overweight and obese men with BMI up to 39 kg/m2 does not significantly influence endocrine testicular function., Luboslav Stárka, Martin Hill, Hana Pospíšilová, Michaela Dušková., and Obsahuje bibliografii
b1_The aim of our study was to compare the responses of heart rate variability (HRV) with two di fferent types of hormonal substitution therapy (HT) in post-menopausal women (cross-sectional study) and to reveal an effect of HT shortly after beginning of its administration (f ollow-up study). To elucidate the influence of menopause and effects of different protocols of a HT on autonomic control of heart rate, we evaluated the heart rate variability (HRV) in 5 groups: premenopausal women (n=140), postmenopausal women without HT (n=360), women on HT with conjugated estrogen only (n =168), women on continuous combined estrogen-progesterone HT (n=117), and men (n=140). Frequency-domain of short-term stationary R-R intervals was performed to evaluate the total variance, low frequency power (LF; 0.04-0.15 Hz), high freque ncy power (HF; 0.15-0.40 Hz), portion of low frequency power (LF%) and ratio of LF to HF (LF/HF). Significantly lower portion of the LF was found in premenopausal women [46.9 (±2.7) nu] when compared to untreated postmenopausal wome n [54.3 (±2.9) nu] and men [55.2 (±3.0) nu]. Treatment by estrogen only was proved to decrease the LF% [40.1 (±2.1) nu] while no effect on HRV was observed in women treated with combination of estrogen and progesterone [57.2 (±3.1) nu]. Also the HF was lower in postmenopausal wome n [4.16 (±0.16) ms 2 ] than in premenopausal women [4.79 (±0.22) ms 2 ] and women treated with estrogen only [4.98 (±0.25) ms 2 ] while in women treated with combined hormonal therapy the average value [3.99 (±0.21) ms 2 ] did not significantly differ from that of untreated postmenopausal women. The follow-up study also proved increase of high frequency power already after two months of estrogen substitution therapy [4.86 (±0.14) ms 2 vs. 4.19 (±0.15) ms 2 ]., b2_These results suggest that hi gher vagal modulation of heart rate that seems typical for younger women becomes after menopause similar to that of men. We also proved a positive shift of HRV parameters toward more beneficial values as for a cardiovascular risk in postmenopausal women treated with estrogens but not in those treated by combined estrogen - progesterone substitution therapy., S.-G. Yang, M. Mlček, O. Kittnar., and Obsahuje bibliografii a bibliografické odkazy
The study investigates the effect of administered estrogen on plasma creatine kinase (CK) and lactate dehydrogenase (LD) levels in female ovariectomized rats after downhill running. Rats ovariectomized before sexual maturity were subcutaneously implanted with pellets containing 17β-estradiol or placebo. Three weeks later they were subjected to a 90-min intermittent downhill running protocol. Blood samples were obtained from the jugular vein immediately after and 72 h after exercise for determination of plasma CK, LD and 17β-estradiol levels. A two-way analysis of variance was used for data evaluation. Plasma CK and LD levels were significantly lower (p<0.05) in the estrogen-supplemented, ovariectomized animals which suggests that less muscle damage occurred compared to the controls immediately and 72 h after exercise. Estrogens may have a protective effect on muscle tissue possibly due to their antioxidant and membrane stabilizing properties., S. Sotiriadou, A. Kyparos, V. Mougios, Ch. Trontzos, G. Sidiras, Ch. Matziari., and Obsahuje bibliografii
Effects of ETB receptor stimulation and its subcellular pathways were evaluated in carbachol pre-contracted rabbit iris sphincter muscles (n=51). ETB stimulation with sarafotoxin (SRTX-c; 10-10-10-6 M) was tested in the absence (n=7) or presence of 10-5 M of: BQ-788 (ETB2 receptor antagonist; n=6), L-NA (NOS inhibitor; n=7) or indomethacin (cyclooxygenase inhibitor; n=10). Effects of ETB stimulation by endothelin-1 (ET-1; 10-10–10-7 M) in the presence of an ETA receptor antagonist (BQ-123; 10-5 M; n=7) and of ETB1 stimulation by IRL-1620 (10-10–10-7 M; n=7) were also tested. Finally, the effects of SRTX-c (10 -9 –10 -7 M) in electric field stimulation (EFS) contraction were evaluated (n=7). ETB receptor stimulation by SRTX-c or ET-1 in presence of BQ-123 promoted a concentration-dependent relaxation of the rabbit iris sphincter muscle by 10.8±2.0 % and 9.4±1.8 %, respectively. This effect was blocked by BQ-788 (-2.3±2.0 %), L-NA (4.5±2.3 %) or indomethacin (2.3±2.9 %). Selective ETB1 stimulation by IRL-1620 did not relax the iris sphincter muscle (0.9±5.4 %). EFS elicited contraction was not altered by SRTX-c. In conclusion, ETB receptor stimulation relaxes the carbachol precontracted iris sphincter muscle, an effect that is mediated by the ETB2 receptor subtype, through NO and the release of prostaglandins., A. Rocha-Sousa ... [et al.]., and Obsahuje seznam literatury
The activity of lipoprotein lipase (LPL) is increased after alcohol consumption and can contribute to an increased level of HDL-cholesterol, which is considered to play a key role in the ethanol-mediated protective effect against cardiovascular disease. The increase in HDL-cholesterol concentration can be also due to an ethanol-enhanced synthesis and secretion of apolipoprotein A-I (apo A-I) from hepatocytes. Therefore, the hypothesis that ethanol consumption affects the LPL and apo A-I gene (LPL and APOA1, respectively) expression was tested in male C57BL/6 mice drinking 5 % ethanol or water and fed a standard chow or high-fat (HF) diet for 4 weeks. The LPL expression was determined in the heart, epididymal and dorsolumbal adipose tissues, the APOA1 expression in the liver. Alcohol consumption did not affect lipid and lipoprotein concentrations in the serum. The LPL expression was increased in the heart of mice given ethanol and HF diet compared to mice on chow and ethanol (p<0.001) and was also increased in epididymal fat in mice given ethanol and HF diet compared to mice on water and HF diet (p<0.05). Neither LPL expression in dorsolumbal fat nor APOA1 expression in the liver were affected by ethanol consumption. Our data suggest that ethanol consumption upregulate LPL expression in a tissue- and diet-dependent manner., E. Mudráková, J. Kovář., and Obsahuje bibiografii a bibliografické odkazy
The aim of this study was to investigate the effects of calcium channel blockers on tertbutyl hydroperoxide (TBH) induced liver injury using isolated perfused rat hepatocytes. Rat hepatocytes were immobilized in agarose threads and perfused with Williams E medium. Hepatocyte injury was induced by the addition of tertbutyl hydroperoxide (1 mM) to the perfusion medium 30 min after the addition of either verapamil or diltiazim. Hepatocyte injury was observed by monitoring the functional and metabolic competence of hepatocytes or by ultrastructural morphological examination of hepatocytes. Verapamil (0.5 mM) reduced lactate dehydrogenase leakage in TBH-injured hepatocytes as compared to the controls (154± 11 % vs. 247± 30 %). Lipid peroxides production was reduced after verapamil pretreatment as compared to the controls and oxygen consumption was increased by pretreatment of hepatocytes with verapamil. Verapamil pretreatment increased the protein synthesis activity at both levels of granular endoplasmic reticulum and free polysomes in cytoplasm and decreased ATPase activity. Diltiazem was qualitatively effective as verapamil. It is concluded that in hepatocyte oxidative injury, calcium channel blockers exhibited hepatoprotective properties. The hepatoprotective effect of calcium channel blockers was accompanied by a decrease in ATPase activity, which may implicate a normalization of Ca2+i after TBH intoxication., H. Farghali, E. Kmoníčková, H. Lotková, J. Martínek., and Obsahuje bibliografii
Cardiotoxicity ranks among the most serious adverse effects of some cytostatics. The cardiac effects of repeated i.v. administration of a new antineoplastic agent, dimethoxybenfluron (once a week, 10 administrations), were investigated in rabbits with respect to cardiac function and the release of cardiac troponin T (cTnT). Different doses of dimethoxybenfluron were administered to two groups of animals (12 mg/kg; n = 7 and 24 mg/kg; n = 6) and compared with either a control group (saline 1 ml/kg; n = 6) or a group with experimentally induced cardiomyopathy (daunorubicin 50 mg/m2; n = 13). In daunorubicin-induced cardiomyopathy, cTnT levels in animals with premature deaths were significantly higher (0.31±0.11 mg/l) in comparison with the surviving animals (0.04±0.03 mg/l). However, cardiac TnT levels after the administration of dimethoxybenfluron in both doses were within the physiological range (lower than 0.1 mg/l) during the whole experiment as it was in the control group. The lack of cardiotoxicity of this new antineoplastic drug was supported by the absence of alterations in PEP:LVET ratio, left ventricle dP/dtmax or histological heart examination as well as by the fact that no premature death of animals occurred following repeated administration of dimethoxybenfluron. It is possible to conclude that no signs of cardiotoxicity were observed following repeated i.v. administration of dimethoxybenfluron., J. Macháčková, M. Adamcová, Y. Mazurová, R. Hrdina, M. Nobilis., and Obsahuje bibliografii