The most common etiology of non- syndromic monogenic obesity are mutations in gene for the Melanocortin -4 receptor ( MC485 ) with variable prevalence in different countries (1.2 -6.3 % of obese children). The aim of our study was 1 ) to search for MC4R mutations in obese children in Slovakia and compare their prevalence with other European countries, and 2 ) to describe the phenotype of the mutation carriers. DNA analysis by direct Sanger sequencing of the coding exons and intron/exon boundaries of the MC4R gene was performed in 268 unrelated Slovak children and adolescents with body mass index above the 97 th percentile for age and sex and obesity onset up to 11 years (mean 4.3±2.8 years). Two different previously described heterozygous loss of function MC4R variants (i.e. p.Ser19Alafs*34, p.Ser127Leu) were identified in two obese probands, and one obese (p.Ser19Alafs*34), and one lean (p.Ser127Leu) adult family relatives. No loss of function variants were found in lean controls. The prevalence of loss -of-function MC4R variants in obese Slovak children was 0.7 %, what is one of the lowest frequencies in Europe., D. Stanikova, M. Surova, L. Ticha, M. Petrasova, D. Virgova, M. Huckova, M. Skopkova, D. Lobotkova, L. Valentinova, M. Mokan, J. Stanik, I. Klimes, D. Gasperikova., and Obsahuje bibliografii
Melatonin plays a key role in the circadian timing system. At present, many other functions of melatonin are known. Question remains whether changes in endogenous melatonin may be associated with food intake. Hence, the levels of melatonin, C-peptide and glucose were followed during a daily regimen (16 hours) including standardized food intake using commercial kits. The diurnal profiles of the hormones and serum glucose were evaluated using ANOVA with Period and Subject as independent factors. Pearson’s correlations and using a multiple stepwise backward regression model consisting of the time factor as a polynomial, and serum C-peptide and glucose assessed the correlations between melatonin and the remaining parameters. Our results showed a significant negative correlation between melatonin and C-peptide. The profile of melatonin was physiological, decreasing after wake-up, showing minor changes during the daytime and increasing in the evening. As documented, lesser alterations were indicated in the course of the melatonin daytime profile, which may reflect periodic food intake. Food intake is not the primary factor influencing the melatonin course. While previous studies have mostly considered the protective effect of melatonin in diabetic subjects, our study brought the results suggesting food intake as a factor contributing to daytime melatonin variation in humans. However, the physiological role of melatonin association with food intake in daytime remains in question and should be further investigated., L. Stárka, M. Dušková, B. Rácz, K. Šimůnková, M. Hill, R. Kancheva., and Obsahuje bibliografii a bibliografické odkazy
Hematopoiesis-modulating action of meloxicam, a cyclooxygenase-2 inhibitor, has been evaluated in mice. Increased serum level of granulocyte colony-stimulating factor (G-CSF) after meloxicam administration has been found in sublethally γ-irradiated animals. In further experiments hematopoiesis-stimulating effects of meloxicam and G-CSF given alone or in combination have been investigated. Granulocyte/macrophage progenitor cells counts were used to monitor these effects. Meloxicam and exogenous G-CSF did not act synergistically when given in combination, but could be mutually substituted during their repeated administration. The results suggest a promising possibility of using meloxicam as an auxiliary drug reducing the high costs of G-CSF therapy of myelosuppression., M. Hofer, M. Pospíšil, V. Znojil, J. Holá, A. Vacek, D. Štreitová., and Obsahuje bibliografii a bibliografické odkazy
The Spontaneously Hypertensive Heart Failure (SHHF) rat mimics the human progression of hypertension from hypertrophy to heart failure. However, it is unknown whether SHHF animals can exercise at sufficient levels to observe beneficial biochemical adaptations in skeletal muscle. Thirty-seven female SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function and expression, and glycogen utilization. The SHHFex rats ran a greater distance and duration as compared to the WFex rats (P<0.05), but the WFex rats ran at a faster speed (P<0.05). Skeletal muscle citrate synthase and β-hydroxyacyl-CoA dehydrogenase enzyme activity was not altered in the SHHFex group, but was increased (P<0.05) in the WFex animals. Citrate synthase protein and gene expression were unchanged in SHHFex animals, but were increased in WFex rats (P<0.05). In the WFex animals muscle glycogen was significantly depleted after exercise (P<0.05), but not in the SHHFex group. We conclude that despite robust amounts of aerobic activity, voluntary wheel running exercise was not sufficiently intense to improve the oxidative capacity of skeletal muscle in adult SHHF animals, indicating an inability to compensate for declining heart function by improving peripheral oxidative adaptations in the skeletal muscle., R. L. Schultz, ... [et al.]., and Obsahuje seznam literatury
This review article summarizes the problems of metabolic disorders and nutrition imbalances that often occur in chronic kidney failure (CKF) or following regular dialysis treatment. In this survey, we cover the pathogenesis of these disorders, their clinical consequences, and their association with the most severe complications of chronic kidney failure and dialysis treatment. These complications are primarily at herosclerosis, malnutrition, anemia, hyperparathyroidism, and other serious problems that markedly and negatively affect prognosis and the quality of life of uremic patients. Risk factors for cardiovascular disease are discussed in-depth because cardiovascular disease is the leading cause of death in patients with chronic kidney failure. It is important to pay attention to the development of these complications because early diagnosis and therapy can improve the prognosis for these patients and reduce treatment costs., R. Cibulka, J. Racek., and Obsahuje bibliografii a bibliografické odkazy
b1_Rats with diabetes induced by streptozotocin (STZ) and nicotinamide (NA) are often used in animal studies concerning various aspects of diabetes. In this experimental model, the severity of diabetes is different depending on doses of STZ and NA. Moreover, diabetic changes in rats with STZ-NA-induced diabetes are not fully characte rized. In our present study, metabolic changes and insulin secretion were investigated in rats with diabetes induced by administration of 60 mg of STZ and 90 mg of NA per kg body weight. Four to six weeks after diabetes induction, insulin, glucagon and some metabolic parameters were determined to evaluate the severity of diabetes. Moreover, insulin secretory capacity of pancreatic islets isolated from control and diabetic rats was compared. It was demonstrated that admi nistration of 60 mg of STZ and 90 mg of NA per kg body weight induced relatively mild diabetes, since insulin, glucagon an d other analyzed parameters were only slightly affected in diabetic rats compared with control animals. In vitro studies revealed that insulin secretory response was preserved in pancreatic islets of diabetic rats, however, was lower than in islets of control animals. This effect was observed in the presence of different stimuli. Insulin secretion induced by 6.7 and 16.7 mmol/l glucose was moderately reduced in islets of diabetic rats compared with control islets. In the presence of leucine with glutamine, insulin secretion appeared to be also decreased in islets of rats with STZ-NA-induced diabetes. Insulinotropic action of 6.7 mmol/l glucose with forskolin was also deteriorated in diabetic islets. Moreover, it was demonstrated that at a non-stimulatory glucose, pharmacological depolarization of plasma membrane with a concomit ant activation of protein kinase C evoked significant rise in insulin release in islets of control and diabetic rats., b2_However, in diabetic islets, this effect was attenuated. These results indicate that impairment in insulin secretion in pancreatic islets of rats with mild diabetes induced by STZ and NA result s from both metabolic and nonmetabolic disturbances in these islets., T. Szkudelski, A. Zywert, K. Szkudelska., and Obsahuje bibliografii a bibliografické odkazy
n our study, 213 healthy Czech women aged 20 to 65 years were examined and divided into fully reproductive, premenopausal, menopausal and postmenopausal groups. In all subjects body composition was determined by classical anthropometry and metabolic profile was assessed. A total of 146 subjects completed 3-year longitudinal study. Total and LDL cholesterol increased and ratio HDL/total cholesterol decreased with age (p<0.001), most significantly in menopause. Triacylglycerols increased only up to menopause. HDL had a very slight trend to decrease in menopause and postmenopause. Fasting blood glucose level increased progressively (p<0.001), in postmenopause frequently exceeded normal range. Higher BMI, total fat mass and central fat indices were associated with higher total and LDL cholesterol, triacylglycerols, C-peptide, insulin and fasting blood glucose level (p<0.001; fasting blood glucose level to waist-to-hip ratio: p<0.01) and lower HDL cholesterol (p<0.001). Higher C-peptide and insulin were associated with lower HDL cholesterol and higher triacylglycerols (p<0.001). Fasting glucose correlated with LD L cholesterol (p<0.01). Higher SHBG was associated with higher HDL and lower LDL cholesterol (p<0.001). Hormone replacement treatment was related to lower fasting blood glucose level in postmenopausal women (p<0.01). Oral contraception is suggestive of a positive influence on lipid spectrum by increasing the ratio HDL/total cholesterol. Markers of lipid and carbohydrate metabolism are not only age-related, but they are also related to BMI, total fat mass and central fat indices. Therefore, preventive programs should be focused above all on menopausal women., I. Kosková, R. Petrásek, K. Vondra, M. Dušková, L. Stárka., and Obsahuje bibliografii
Parameters of branched-chain amino acids (BCAA; leucine, isoleucine and valine) and protein metabolism were evaluated using L-[1-14C]leucine and a-keto[1-14C]isocaproate (KIC) in the whole body and in isolated perfused liver (IPL) of rats fed ad libitum or starved for 3 days. Starvation caused a significant increase in plasma BCAA levels and a decrease in leucine appearance from proteolysis, leucine incorporation into body proteins, leucine oxidation, leucine-oxidized fraction, and leucine clearance. Protein synthesis decreased significantly in skeletal muscle and the liver. There were no significant differences in leucine and KIC oxidation by IPL. In starved animals, a significant increase in net release of BCAA and tyrosine by IPL was observed, while the effect on other amino acids was non-significant. We conclude that the protein-sparing phase of uncomplicated starvation is associated with decreased whole-body proteolysis, protein synthesis, branched-chain amino acid (BCAA) oxidation, and BCAA clearance. The increase in plasma BCAA levels in starved animals results in part from decreased BCAA catabolism, particularly in heart and skeletal muscles, and from a net release of BCAA by the hepatic tissue., M. Holeček, L. Šprongl, I. Tilšer., and Obsahuje bibliografii
The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [3 H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [3 H]-DHEAS to [ 3 H]-androstenedione, [3 H]-testosterone, [3 H]-estrone and [ 3 H]-17β-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E1 S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [3 H]-estrone to [3 H]-17β- estradiol. This is the first demonstration that human platelets are able to import DHEAS and E1 S using the OATP family and to convert DHEAS to active DHEA, and to transform E1 S to 17β- estradiol., A. Garrido ... [et al.]., and Obsahuje seznam literatury